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evolution
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monomeric GTPases belong to the RAS superfamily
evolution
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Rac and RhoA belong to the Rho family of GTPases, small monomeric G proteins
evolution
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Rap GTPase is a member of the Ras superfamily
evolution
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Rap GTPase is a member of the Ras superfamily
evolution
Alp41/Arl2 is a highly conserved small GTPase
evolution
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enzyme Ryh1 belongs to the Rab-family GTPases
evolution
Rab proteins are members of the Ras superfamily of GTPases that switch between GDP-bound (inactive) and GTP-bound (active) forms
evolution
Ras homologue enriched in the brain (Rheb) belongs to the Ras superfamily, sharing high homology with human Rap2, yeast RAS1, and human H-Ras
evolution
Ras proximity 1 (Rap1) belongs to the Ras superfamily of GTPases that cycle between GTP-bound active and GDPbound inactive forms through GEFs and GAPs
evolution
the enzyme belongs to the Ras superfamily
evolution
the enzyme belongs to the Rho GTPase family of enzymes
evolution
the enzyme belongs to the superfamily of small GTPase proteins
evolution
Arf6 is a member of the Arf family of small GTPases
evolution
Drosophila Rap1 is a member of the Ras family of GTPases
evolution
the enzyme belongs to the Rac/ROP family small GTPases
evolution
the subfamily of Ras-like small GTPases contains numerous members including classical Ras (H-, K-, and N-Ras), R-Ras, TC21/R-Ras2, MRas/R-Ras3, DexRas1/RasD1, RalA/B, Rheb, Rit, Rin, Rap1 and Rap2, and atypical kappaB-Ras1 and kappaB-Ras2
evolution
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Ypt1p is a member of the Rab family of small GTPases. A large number of small GTPases belonging to the Rab family play a role in vesicular trafficking
evolution
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Alp41/Arl2 is a highly conserved small GTPase
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evolution
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Ras proximity 1 (Rap1) belongs to the Ras superfamily of GTPases that cycle between GTP-bound active and GDPbound inactive forms through GEFs and GAPs
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evolution
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Drosophila Rap1 is a member of the Ras family of GTPases
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evolution
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Arf6 is a member of the Arf family of small GTPases
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evolution
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the enzyme belongs to the Rho GTPase family of enzymes
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evolution
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the enzyme belongs to the Rac/ROP family small GTPases
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malfunction
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in cultured human microvascular endothelial cells, knockdown of either Rap1a or 1b appears to diminish adhesion to the extracellular matrix and impair cell migration, and also increases permeability. Loss of Rap1a or 1b unexpectedly blocked angiogenesis by abolishing the angiogenic response to FGF2 or to VEGF, leading to an inability for these cells to form tubular structures. Ablation of either isoforms leads to decrease in FGF-2 mediated ERK, p38 and Rac activation which are all important angiogenesis signaling molecules. Overexpressing activated Rap 1a in dermal microvascular endothelial cells show defective angiogenesis through regulation of thrombospondin-1
malfunction
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overexpression of dominant-negative Sar1 and Rab1b mutants and the use of siRNAs impair autophagosome generation as determined by LC3 puncta formation and light chain 3 (LC3)-II processing. Recombinant expression of Sar1 mutants H79G or Sar1 T39N induce Golgi fragmentation
malfunction
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the loss of Rap1b leads to deficiencies both in B cell migration and in adhesion. Platelets from Rap1b null mice exhibit defective aggregation in response to integrin stimulation. These mice exhibit protection from arterial thrombosis and provide an independent role for this Rap1 isoform
malfunction
a dominant active mutant of Cdc42 promotes the formation of invadopodia. Small interfering RNA-mediated Fgd1 knockdown inhibits TGFbeta-induced Cdc42 activation and reduces podosome formation and associated extracellular matrix degradation
malfunction
all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, overview
malfunction
all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, septum defect and nuclear division phenotype of DELTAFgrho4 deletion mutant, overview
malfunction
all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. FgRac1 deletion mutants display a precocious, multi-site germ tube formation as well as hyperbranching of hyphae. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, overview
malfunction
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deletion of Cdc42 in mature B cells results in an antibody response of reduced magnitude and lower affinity to soluble T cell-dependent antigen. B cells that lack Cdc42 remain dominant for 2 weeks postinduction with tamoxifen, following which Cdc42-sufficient B cells gradually dominate with very few Cdc42-deficient B cells being detected after 6 weeks. Deletion of Cdc42 in mature B cells alters their ability to activate T cells. B cells that lack Cdc42 fail to form long protrusions on Ab-coated surfaces. Reduced spreading and upregulation of CIP4 in Cdc42-deficient B cells. Deletion of Cdc42 in B cells leads to impaired humoral immune response, phenotype, overview
malfunction
Dysfunction of hRAB37 or TIMP1 abrogates metastasis suppression
malfunction
ectopic expression of active RhoA suppresses podosome formation in response to phorbol ester by global inhibition of actin turnover
malfunction
expression of constitutively active RhoA in primary culture of spinal motoneurons also drastically reduces high-voltage-activated Ca2+ current amplitude
malfunction
if Tbc1 loses its GAP activity as in the tbc1-11 mutant, Alp41 will no longer be converted from its active, GTP-bound state to the inactive, GDP-bound state. Overproduction of GTP or GDP form of Alp41 is toxic to the cell
malfunction
increased expression of GCF2 is found in human chemotherapeutic agent cisplatin-resistant cells, and overexpression in GCF2-transfected cells results in loss of RhoA expression and disruption of the actin-filamin network. The membrane transporter MRP1 is internalized from the cell surface into the cytoplasm, rendering cells sensitive to doxorubicin by more than 10fold due to increased accumulation of doxorubicin in the cells. The GCF2 transfectants also show reduced accumulation of cisplatin and increased resistance. siRNA targeted to GCF2 suppresses the expression of GCF2 in cisplatin-resistant cells, reactivates RhoA expression, and restores the fine structure of actin microfilaments. MRP1 is also relocated to the cell surface. siRNA targeted to RhoA increased resistance 3fold in KB-3-1 and KB-CP.5 cells. Phenotypes, overview. Silencing RhoA increases resistance against cisplatin
malfunction
misregulation of the enzyme is involved in several diseases, especially cancer
malfunction
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overexpression of Rad in cells lowers both the basal and TNFalpha-stimulated transcriptional activity of NFkappaB. Compared with control cells, Rad-overexpressing cells display more cytoplasmic distribution of the NFkappaB subunit RelA/p65,while Rad knockdown cells have higher levels of nuclear RelA/p65. Depleting Rad does not affect the kinetics of TNFalpha-induced IkappaB degradation. Rad depletion alters the expression of an array of NFkappaB target genes, including upregulating MMP9, depletion of Rad enhances MMP9 expression and cell invasion. Knockdown of Rad expression in cells increases both basal and TNFalpha-stimulated MMP9 activities and cell invasion
malfunction
Rac1-deficient macrophages show impaired podosome formation with fewer cells displaying podosomes that lack the adhesion ring, but migrate at a speed similar to that of wild-type macrophages
malfunction
Rac2 deficiency results in complete loss of podosomes in macrophages
malfunction
Rap1b deficiency increases neutrophil transmigration, Rap1b loss promotes transendothelial migration via transcellular route. Rap1b-deficient mice exhibits enhanced neutrophil recruitment to inflamed lungs and enhanced susceptibility to endotoxin shock. Rap1b-/- neutrophils exhibit enhanced chemokinesis and chemotaxis. Rap1b deficiency promotes the transcellular route of diapedesis through endothelial cell. Increased transcellular migration of Rap1b-deficient neutrophils in vitro is selectively mediated by enhanced PI3K-Akt activation and invadopodia-like protrusions. Akt inhibition in vivo suppresses excessive Rap1b-deficient neutrophil migration and associated endotoxin shock. Pharmacological inhibition of Akt activation rescued Rap1b-/- neutrophil phenotype. Rap1a expression does not compensate for Rap1b loss in blood cells. Phenotype, overview
malfunction
RNAi knockdown of Trypanosom brucei Arl6 results in shortening of the trypanosome flagellum without loss of motility
malfunction
upon long term treatment with CNF1, RhoB-/- mouse embryonic fibroblasts exhibit DNA fragmentation, phosphatidylserine exposure, and loss of membrane integrity, while RhoB+/- MEFs persist as bi-nucleated (tetraploid) cells without any signs of cell death
malfunction
ARF6Q67L promotes spontaneous metastasis from significantly smaller primary tumors than PTENNULL, implying an enhanced ability of ARF6-GTP to drive distant spread. ARF6Q67L tumors show upregulation of Pik3r1 expression, which encodes the p85 regulatory subunit of PI3K. Tumor cells expressing ARF6Q67L displays increased PI3K protein levels and activity, enhances PI3K distribution to cellular protrusions, and increases AKT activation in invadopodia. Aberrant ARF6 activation in human melanoma samples is associated with reduced survival
malfunction
both knockdown and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-kappaB activity and inflammatory gene expression. Silencing of Rap2a impairs LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-kappaB activity. Overexpression of Rap2a does also lead to marked inhibition of NF-kappaB activation induced by LPS, Pam3CSK4, and downstream TLR signaling molecules. Dysregulation of Rap2a expression in an inflammatory context may significantly alter the status of NF-kappaB activation
malfunction
gain-of-function studies using dominant-negative and constitutively active forms of Rap1 indicate that Rap1 contributes to axonal growth and guidance
malfunction
knockdown of Rab13 blocks pterostilbene-induced mTOR inhibition and autophagy, whereas overexpression of the GTP-containing active form of Rab13 induces mTOR inhibition and autophagy in HUVECs. Upregulation of the active form of small GTPase Rab13 promotes macroautophagy in vascular endothelial cells. Knockdown of Grb2 suppresses pterostilbene or upregulation of the active form of Rab13-induced autophagy. Knockdown of Rab13 inhibits the digestion of cytoplasmic components in pterostilbene-treated HUVECs numerous autophagosome- or autolysosome-like vesicular structures
malfunction
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RNA interference of Pc-Rac1 affects the mRNA expression levels of immune-related genes lectin, Toll, crustin, TNF, ALF and cactus
malfunction
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temperature-sensitive growth phenotype of the ypt1-G80D mutant strain. Complete knockout of the YPT1 gene in yeast is lethal. Abrogation of heat-shock-induced Ypt1p chaperone function by the G80D mutation lowers cell viability largely by hindering metabolism and cellular energy generation. Mutant Ypt1pG80D retains GTPase activity but loses molecular chaperone activity
malfunction
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if Tbc1 loses its GAP activity as in the tbc1-11 mutant, Alp41 will no longer be converted from its active, GTP-bound state to the inactive, GDP-bound state. Overproduction of GTP or GDP form of Alp41 is toxic to the cell
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malfunction
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deletion of Cdc42 in mature B cells results in an antibody response of reduced magnitude and lower affinity to soluble T cell-dependent antigen. B cells that lack Cdc42 remain dominant for 2 weeks postinduction with tamoxifen, following which Cdc42-sufficient B cells gradually dominate with very few Cdc42-deficient B cells being detected after 6 weeks. Deletion of Cdc42 in mature B cells alters their ability to activate T cells. B cells that lack Cdc42 fail to form long protrusions on Ab-coated surfaces. Reduced spreading and upregulation of CIP4 in Cdc42-deficient B cells. Deletion of Cdc42 in B cells leads to impaired humoral immune response, phenotype, overview
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malfunction
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Rap1b deficiency increases neutrophil transmigration, Rap1b loss promotes transendothelial migration via transcellular route. Rap1b-deficient mice exhibits enhanced neutrophil recruitment to inflamed lungs and enhanced susceptibility to endotoxin shock. Rap1b-/- neutrophils exhibit enhanced chemokinesis and chemotaxis. Rap1b deficiency promotes the transcellular route of diapedesis through endothelial cell. Increased transcellular migration of Rap1b-deficient neutrophils in vitro is selectively mediated by enhanced PI3K-Akt activation and invadopodia-like protrusions. Akt inhibition in vivo suppresses excessive Rap1b-deficient neutrophil migration and associated endotoxin shock. Pharmacological inhibition of Akt activation rescued Rap1b-/- neutrophil phenotype. Rap1a expression does not compensate for Rap1b loss in blood cells. Phenotype, overview
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malfunction
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gain-of-function studies using dominant-negative and constitutively active forms of Rap1 indicate that Rap1 contributes to axonal growth and guidance
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malfunction
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all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, septum defect and nuclear division phenotype of DELTAFgrho4 deletion mutant, overview
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malfunction
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all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, overview
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malfunction
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all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. FgRac1 deletion mutants display a precocious, multi-site germ tube formation as well as hyperbranching of hyphae. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, overview
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metabolism
a complex regulatory pathway downstream from GCF2 involves the small GTPase RhoA, actin/filamin dynamics, and membrane protein trafficking, overview
metabolism
high-voltage-activated Ca2+ channels are known regulators of synapse formation and transmission and play fundamental roles in neuronal pathophysiology. Small GTPases of Rho and RGK families, via their action on both cytoskeleton and Ca2+ channels are key molecules for these processes
metabolism
photoreceptor R7 is specified by the combined actions of the receptor tyrosine kinase (RTK) and Notch (N) signaling pathways. These pathways interact in a complex manner that includes antagonistic effects on photoreceptor specification and involve the small GTPase Rap. RTK promotes the photoreceptor fate, whereas N inhibits it
metabolism
Rac/Rop proteins are Rho-type small GTPases that act as molecular switches in plants. They are key components in many major plant signaling pathways, such as innate immunity, pollen tube growth, and root hair formation
metabolism
RhoGTPases are involved in podosome assembly and sequential mechanism for invadopodium formation, regulation, detailed overview
metabolism
six Rab isoforms are involved in regulating Golgi morphology in HeLa-S3 cells
metabolism
the tubulin cofactor pathway consists of a specific set of chaperones that aid the folding of alpha- and beta-tubulin monomers into a functional heterodimer, with the introduction of cofactor C, GTP hydrolysis occurs, triggering the release of the newly folded alpha/beta-tubulin heterodimer for addition to the plus end of the microtubule, modeling of the final stages of the tubulin cofactor pathway that includes a dual role for both Tbc1 and Alp1D in opposing regulation of the microtubule. Alp41 GTPase interacts with cofactor D, Alp1D, only when bound to GDP
metabolism
ACAP3, the GTPase-activating protein specific to the small GTPase Arf6, regulates neuronal migration in the developing cerebral cortex. ACAP3 is involved in neuronal migration in the developing cerebral cortex of mice. Knockdown of ACAP3 in the developing cortical neurons of mice in utero significantly abrogates neuronal migration in the cortical layer, which is restored by ectopic expression of wild-type ACAP3, but not by its GAP-inactive mutant
metabolism
an increasing number of Rab GTPases have been shown to play either critical or accessory roles in various stages of autophagy. Rab1, Rab4, Rab5, Rab11, Rab12, Rab17, Rab23, Rab26, Rab30 and Rab32 participate in autophagosome formation. Rab13 is required for pterostilbene-induced autophagy
metabolism
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identification of diverse putative Ypt1p-regulatory proteins under heat-shock, overview
metabolism
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Rac1 can interact with the PBD domain of p21-activated kinase 1 (PAK1)
metabolism
Rap2a is activated by lipopolysaccharide in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b is sufficient to induce, it is not fully required for Rap2a activation. Dysregulation of Rap2a expression in an inflammatory context may significantly alter the status of NF-kappaB activation
metabolism
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the tubulin cofactor pathway consists of a specific set of chaperones that aid the folding of alpha- and beta-tubulin monomers into a functional heterodimer, with the introduction of cofactor C, GTP hydrolysis occurs, triggering the release of the newly folded alpha/beta-tubulin heterodimer for addition to the plus end of the microtubule, modeling of the final stages of the tubulin cofactor pathway that includes a dual role for both Tbc1 and Alp1D in opposing regulation of the microtubule. Alp41 GTPase interacts with cofactor D, Alp1D, only when bound to GDP
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metabolism
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ACAP3, the GTPase-activating protein specific to the small GTPase Arf6, regulates neuronal migration in the developing cerebral cortex. ACAP3 is involved in neuronal migration in the developing cerebral cortex of mice. Knockdown of ACAP3 in the developing cortical neurons of mice in utero significantly abrogates neuronal migration in the cortical layer, which is restored by ectopic expression of wild-type ACAP3, but not by its GAP-inactive mutant
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physiological function
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Rac and RhoA belong to the small, monomeric G proteins of the Rho family of GTPases, that, when activated, initiate a signaling cascade that reorganizes the neuronal cytoskeleton. Rho GTPases regulate cellular morphogenesis through direct interactions with actin and microtubule-organizing proteins. Rho GTPases are cycling between the inactive GDP-bound and the active GTP-bound forms is controlled by guanine nucleotide exchange factors, GTPase activating proteins, and guanine nucleotide dissociation inhibitors
physiological function
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Rap1A and Rap1B have differing roles in the cardiovasculature. Activation of Rap1a and 1b in various cell types of the cardiovasculature lead to alterations in cell attachment, migration and cell junction formation. Rap1b is necessary for proper development, homing and T cell dependant immunity. Rap1b protein regulates the SERCA 3b-associated Ca2+ pool through its cAMP-dependent phosphorylation, and therefore plays a role in the transition between platelet activation and inhibition. Whereas Rap1a and 1b appear to be key regulators in differing cell types of the blood, neutrophils and platelets, both appear to contribute to the normal function of endothelial cells and to angiogenesis. In smooth muscle cells, Rap1 may elicit a protective response to maintain vessel wall integrity in response to cellular stress
physiological function
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Sar1 and Rab1b are monomeric GTPases that control traffic from the endoplasmic reticulum to the Golgi, Sar1 is responsible for export from the endoplasmic reticulum and is required for the initial steps in the secretory pathway, activity of both proteins is required for autophagosome formation under starvation or rapamycin treatment
physiological function
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small monomeric GTPases have a function in fruit development and ripening. PpARF and PpRAB of the A and D clades are putatively controlling the exocytic delivery of cell wall components and modifying enzymes
physiological function
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the GTP-bound Rap mediates signaling by associating with, and activating effector proteins. Whereas Rap1a and 1b appear to be key regulators in differing cell types of the blood, neutrophils and platelets, both appear to contribute to the normal function of endothelial cells and to angiogenesis. Endothelial cell junctional proteins are involved in regulating vascular permeability. This dynamic regulation is regulated in part by Rap1 in response to cAMP activation through Epac1. In cultured human umbilical vein endothelial cells activation of Epac1-Rap1 by cAMP enhances endothelial barrier function by altering actin cytoskeleton organization, activating microtubule growth and results in a redistribution of adherens junctional proteins involving MAGI-1 protein. Rap1a and b are involved in the activation of beta1-integrins in endothelial cells and play a key role in integrin dependent angiogenic functions such as sprouting, tube formation, migration and adhesion. In smooth muscle cells, Rap1 may elicit a protective response to maintain vessel wall integrity in response to cellular stress
physiological function
a pathway involving GTPase Rac1 positively regulates the activity of the rhoB promoter and RhoB expression. Critical role of transcriptional activation in CNF1-induced RhoB expression. Regulation of the rhoB promoter, overview. RhoB dependent suppression of CNF1-induced polyploidy and cell death
physiological function
a pathway involving GTPase Rac1 positively regulates the activity of the rhoB promoter and RhoB expression. The cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivatingRho/Ras proteins but also by the Rac1-activating toxin CNF1. Critical role of transcriptional activation in CNF1-induced RhoB expression. Regulation of the rhoB promoter, overview
physiological function
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activity of Ypt7p in proteoliposome lipid mixing: Ypt7p is required for the lipid mixing of proteoliposomes lacking cardiolipin [1,3-bis-(sn-3-phosphatidyl)-sn-glycerol]. Omission of other lipids with negatively charged and/or small head groups does not cause Ypt7p dependence for lipid mixing. Disruption of cardiolipin synthase, CRD1, does not alter dependence on Rab GTPases for vacuole fusion. Lipid mixing of proteoliposomes lacking cardiolipin is completely dependent on the presence of Ypt7p. The recruitment of the HOPS, homotypic fusion and protein sorting, complex to membranes is the main function of enzyme Ypt7p. Ypt7p therefore must stimulate membrane fusion by a mechanism that is in addition to recruitment of HOPS to the membrane. Lipid mixing required soluble NSF (N-ethylmaleimide-sensitive factor)-attachment protein receptor proteins, Sec18p and Sec17p (yeast NSF and alpha-SNAP) and the HOPS (homotypic fusion and protein sorting)-class C vacuole protein sorting complex, but not the vacuolar Rab GTPase Ypt7p
physiological function
cell adhesion and migration are regulated through the concerted action of cytoskeletal dynamics and adhesion proteins, the activity of which is governed by RhoGTPases. Specific RhoGTPase signaling requires spatio-temporal activation and coordination of subsequent protein-protein and protein-lipid interactions. The nature, location and duration of these interactions are dependent on polarized extracellular triggers, such as cell-cell contact, and intracellular modifying events, such as phosphorylation. RhoA, RhoB, and RhoC are highly homologous GTPases that, however, succeed in generating specific intracellular responses
physiological function
dual role of fission yeast Tbc1/cofactor C orchestrates microtubule homeostasis in tubulin folding and acts as a GTPase activating protein for GTPase Alp41/Arl2, Tbc1 and Alp41 directly interact, mutational analysis, overview. Tbc1 is the cofactor C involved in correct folding of alphabeta-tubulin heterodimers, critical for microtubule dynamics. The expression of GDP- or GTP-bound Alp41 shows a microtubule loss phenotype, continuous cycling between these forms seems important for its functions. Alp41 GTPase interacts with cofactor D, Alp1D, only when bound to GDP, GDP-bound Alp41 sequesters overproduced Alp1D from microtubules and rescues abnormal microtubule structures
physiological function
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enzyme Der is an essential and widely conserved GTPase that assists assembly of a large ribosomal subunit in bacteria. Enzyme Der associates specifically with the 50S subunit in a GTP-dependent manner and the cells depleted of GTPase Der accumulate the structurally unstable 50S subunit, which dissociates into an aberrant subunit at a lower Mg2+ concentration. The enzyme Der is an essential and ubiquitous protein in bacteria
physiological function
enzyme Der is an essential and widely conserved GTPase that assists assembly of a large ribosomal subunit in bacteria. Enzyme Der associates specifically with the 50S subunit in a GTP-dependent manner and the cells depleted of GTPase Der accumulate the structurally unstable 50S subunit, which dissociates into an aberrant subunit at a lower Mg2+ concentration. The enzyme Der is an essential and ubiquitous protein in bacteria
physiological function
enzyme Der is an essential and widely conserved GTPase that assists assembly of a large ribosomal subunit in bacteria. Enzyme Der associates specifically with the 50S subunit in a GTP-dependent manner and the cells depleted of GTPase Der accumulate the structurally unstable 50S subunit, which dissociates into an aberrant subunit at a lower Mg2+ concentration. The enzyme Der is an essential and ubiquitous protein in bacteria
physiological function
enzyme Der is an essential and widely conserved GTPase that assists assembly of a large ribosomal subunit in bacteria. Enzyme Der associates specifically with the 50S subunit in a GTP-dependent manner and the cells depleted of GTPase Der accumulate the structurally unstable 50S subunit, which dissociates into an aberrant subunit at a lower Mg2+ concentration. The enzyme Der is an essential and ubiquitous protein in bacteria
physiological function
Rab small GTPases are master regulators of membrane trafficking and guide vesicle targeting. Rab proteins transport cargo proteins to target membrane, organelle and cellular compartment to coordinate the cell membrane dynamics, cytoskeleton organization, signal transduction and membrane trafficking. Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 (TIMP1) for exocytosis and thus suppresses tumour metastasis in a nucleotide-dependent manner. hRAB37 is involved in transportation of exocytotic vesicles and is involved in the exocytotic pathway of nascent secretory protein from the Golgi to the plasma membrane but not in the recycling endosome-mediated secretory pathway. Tissue inhibitor of metalloproteinase 1 is a secreted protein that inhibits MMPs and extracellular matrix turnover thereby decreasing cell motility. Rab-controlled trafficking pathways are altered during tumorigenesis. Tissue inhibitor of metalloproteinase 1 (TIMP1), a secreted glycoprotein that inhibits extracellular matrix turnover, is a cargo of hRAB37. hRAB37 regulates the exocytosis of TIMP1 in a nucleotide-dependent manner to inactivate matrix metalloproteinase 9 (MMP9) migration axis in vitro and in vivo
physiological function
Rab small GTPases are membrane trafficking proteins. Rab1A non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule
physiological function
Rab small GTPases are membrane trafficking proteins. Rab1B non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule
physiological function
Rab small GTPases are membrane trafficking proteins. Rab2A non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule
physiological function
Rab small GTPases are membrane trafficking proteins. Rab2B non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule. Golgi-associated Rab2B interactor-like 4 (GARI-L4) is a Golgi-resident Rab2B-specific binding protein whose knockdown also induces fragmentation of the Golgi like the knockdown of Rab2B. Effector protein GARI-L4 is required for the compacted Golgi morphology in HeLa-S3 cells
physiological function
Rab small GTPases are membrane trafficking proteins. Rab6A non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule
physiological function
Rab small GTPases are membrane trafficking proteins. Rab8B non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule
physiological function
Rac/Rop protein OsRac1 plays an important role in regulating the production of reactive oxygen species by the NADPH oxidase OsRbohB during innate immunity. Direct OsRac1-OsRbohB interactions activate NADPH oxidase in plants
physiological function
Rac1 is one of the biologically important gene in coronary heart diseases. Rac directly regulates the activity of the NADPH oxidase and the generation of reactive oxygen species (ROS), important players of cardiovascular disorder
physiological function
Rac1 is one of the biologically important genes in coronary heart diseases, i.e. cardiomyocyte hypertrophy and atherosclerosis, overview. Rac directly regulates the activity of the NADPH oxidase and the generation of reactive oxygen species (ROS), important players of cardiovascular disorder. Rac1 facilitates the formation of the lamellipodia structures by initiating peripheral actin polymerization through the Arp2/3 complex that is activated by either the Wiskott-Aldrich syndrome protein (WASP) family or the WAVE (WASP with a V-domain) family proteins. Rac1, through the calmodulin-binding GAP, that is enriched at the leading edge of migrating cells, influences the organization of microtubules, and thus cell shape and polarity. In addition to the cytoskeletal and microtubules effects, Rac1 regulates several signal transduction pathways that lead to alterations in gene expression. Cellular effects of Rac1 activation in cardiomyocytes, smooth muscle cells, endothelial cells, and leukocytes, overview
physiological function
Rac1 is one of the biologically important genes in coronary heart diseases. Rac directly regulates the activity of the NADPH oxidase and the generation of reactive oxygen species (ROS), important players of cardiovascular disorder
physiological function
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Rad is a Ras-related small GTPase shown to inhibit cancer cell migration, and its expression is frequently lost in lung cancer cells. Rad can negatively regulate the NFkappaB pathway. Rad-mediated regulation of NFkappaB is through an IkappaB-independent mechanism. Expression of a nucleus-localized mutant Rad is sufficient to inhibit the NFkappaB transcriptional activity, whereas expressing the scaffolding protein 14-3-3gamma to retain Rad in the cytoplasm alleviates the suppressive effect of Rad on NFkappaB. The Rad-p65 interaction primarily occurs in the nucleus. Rad may directly impede the interaction between RelA/p65 and DNA. Role of nuclear Rad in inhibiting the NFkappaB pathway function
physiological function
remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, and guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly
physiological function
remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, and guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly. Osteoclasts generated from the Rac double knockout mouse are devoid of podosomes and sealing zone, and show impaired bone resorption capacities. Rac1 and Rac2 have overlapping roles in podosome assembly and sealing zone-like structure formation by localizing Arp2/3 at podosome sites during osteoclastogenesis.. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation
physiological function
remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, e.g. Dock 5, FARP2 (FRG), a Dbl family GEF specific for Rac1. And guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly. Osteoclasts generated from the Rac double knockout mouse are devoid of podosomes and sealing zone, and show impaired bone resorption capacities. Rac1 and Rac2 have overlapping roles in podosome assembly and sealing zone-like structure formation by localizing Arp2/3 at podosome sites during osteoclastogenesis. Dock5 and Vav3 regulate Rac1 activation at distinct locations in osteoclasts and at different phases of the bone-resorption cycle
physiological function
remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, e.g. Fgd1 is the GEF mediating Cdc42 activation and subsequent podosome formation in TGFbeta-stimulated BAE cells. And guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly. Essential role of Cdc42 in podosome formation, Cdc42 stands as a central player in the regulation of podosome dynamics as it orchestrates podosome actin polymerization via its canonical effector, WASp. When activated by a GEF, Cdc42 binds to WASp. This binding, together with phosphorylation of WASp on tyrosine, induces a dramatic conformational change. The hydrophobic core is disrupted, releasing the verprolin homology domain-cofilin homology domain-acidic region domain (VCA domain) and enabling its interaction with the Arp2/3 complex, thereby promoting actin nucleation. Constitutively active Cdc42 induces podosome formation in vascular smooth muscle cells
physiological function
requirement for rap gene function in photoreceptor R7, localization of rap gene activity, overview. Overactivity of Ras GTPase activating proteins or underactivity of Ras guanine exchange factors, among other possibilities might account for the limitation in the Ras pathway
physiological function
Rheb acts as a molecular switch in several cellular processes, such as misfolded protein metabolism, cellular apoptosis, vesicle formation and myogenesis. The Ras homologue enriched in brain (Rheb) regulates diverse cellular functions by modulating its nucleotide-bound status. Deacetylated alphabeta-tubulin acts as a positive regulator of Rheb GTPase through increasing its GTP-loading, regulatory mechanism of Rheb, overview. Modulation of both soluble and acetylated alphabeta-tubulin levels affects the level of GTP-bound Rheb. This occurs in the mitotic phase in which the level of acetylated alphabeta-tubulin is increased but that of GTP-bound Rheb is decreased. Rheb is an upstream key activator for the mammalian target of rapamycin (mTOR) complex 1 (mTORC1), which has a central role in cell growth by regulating protein synthesis, through modulating mTOR kinase activity. Tubulin-mediated Rheb regulation, detailed overview
physiological function
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. FgRac1 interacts with FgCla4 via its PBD domain and genetically acts upstream of FgCla4 to affect hyphal growth and conidiation. Isozyme FgRac1 is important for hyphal growth and conidiation. FgRac1 negatively controls deoxynivalenol production. FgCla4 is a downstream target of FgRac1, but is dispensable for sexual development. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Isozyme FgRHO1 is essential for fungal survival. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Isozyme FgRho3 demonstrates functions only in vegetative growth and conidiation. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Rho GTPase FgRho2 is multifunctional and is involved in sexual development and pathogenesis. FgRho2 is involved in cell wall integrity. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. The Rho GTPase FgCdc42 is multifunctional and is involved in sexual development and pathogenesis. Isozyme FgCdc42 is important for hyphal growth and conidiation. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. The Rho GTPase FgRho4 is multifunctional and is involved in sexual development and pathogenesis. While FgRho4 is involved in cell wall integrity, and FgRho4 shows a role in nuclear division and septum formation. FgRho4 is also important for hyphal growth and conidiation. Isozyme FgRho4 plays a positive role in deoxynivalenol production. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
RhoA inhibits HVA CaV2 Ca2+ channels in a CaVbeta subunit-independent manner, recombinant RhoA activity reduces Ba2+ currents through CaV2.1, CaV2.2 and CaV2.3 Ca2+ channels independently of CaVbeta subunit. This inhibition occurs independently of RGKs activity and without modification of biophysical properties and global level of expression of the channel subunit. High-voltage-activated Ca2+ channels regulation by RhoA might govern synaptic transmission during development and potentially contribute to pathophysiological processes when axon regeneration and growth cone kinetics are impaired. Effects of RhoA on CaV2 trafficking to the plasma membrane, regulation of Ca2+ channel expression and activity by small GTPases, overview
physiological function
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role of intrinsic expression of Cdc42 by mature B cells in their activation and function, Cdc42 expression in B cells is essential for efficient IL-2 secretion of CD4+ T cells in cognate T-B cell interaction
physiological function
small GTPase Rap1 regulates cell migration through regulation of small GTPase RhoA activity in response to transforming growth factor-beta1. GTP-RhoA and GTP-Rap1 levels are reciprocally regulated in a time-dependent manner following TGF-beta1 stimulation. Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states. In the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position. GTP-binding to small GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), and hydrolysis of the bound GTP is accelerated by GTPase activating proteins (GAPs), Downstream effector proteins of Rap1, including RapL, AF6, and ARAP3 transmit the activated Rap1 signals within the cells. Rap1 regulates GTPase RhoA activity, but RhoA does not regulate the Rap1 activity
physiological function
small GTPase Rap1 regulates cell migration through regulation of small GTPase RhoA activity in response to transforming growth factor-beta1. GTP-RhoA and GTP-Rap1 levels are reciprocally regulated in a time-dependent manner following TGF-beta1 stimulation. Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states. In the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position. GTP-binding to small GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), and hydrolysis of the bound GTP is accelerated by GTPase activating proteins (GAPs). Downstream effector proteins of Rap1, including RapL, AF6, and ARAP3 transmit the activated Rap1 signals within the cells. Rap1 regulates GTPase RhoA activity, but RhoA does not regulate the Rap1 activity
physiological function
small GTPases are central signaling proteins in all eukaryotic cells acting as a molecular switches that are active in the GTP-state and inactive in the GDP-state. GTP-loading is highly regulated by guanine nucleotide exchange factors
physiological function
the cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivatingRho/Ras proteins but also by the Rac1-activating toxin CNF
physiological function
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the enzyme Ryh1 activates the target of rapamycin complex 2, TORC2, a protein kinase complex that is required for the TORC2-Gad8 pathway, which is essential for growth under glucose-limited conditions. the nucleotide-binding state of Ryh1 is regulated in response to glucose mediating the nutrient signal to TORC2. In glucose-rich growth media, the GTP-bound form of Ryh1 induces TORC2-dependent phosphorylation of Gad8, a downstream target of TORC2 in fission yeast. Upon glucose deprivation, Ryh1 becomes inactive, which turns off the TORC2-Gad8 pathway. During glucose starvation, Gad8 phosphorylation by TORC2 gradually recovers independently of Ryh1, implying an additional TORC2 activator that is regulated negatively by glucose. The paired positive and negative regulatory mechanisms may allow fine-tuning of the TORC2-Gad8 pathway
physiological function
the small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation. The inhibitory action of Rap1b on PI3K signaling may be mediated by activation of phosphatase SHP-1. Role for Rap1b as a key suppressor of neutrophil migration and lung inflammation, which may represent an unappreciated regulatory pathway of neutrophil-related aberrant inflammatory responses. Rap1b inhibits Akt activation via CD11b outside-in signaling, Rap1b negatively regulates PI3K-Akt signaling via the phosphatase SHP-1
physiological function
the transcription factor GCF2 is an upstream repressor of the small GTPAse RhoA, regulating membrane protein trafficking, sensitivity to doxorubicin, and resistance to cisplatin. GC-binding factor 2 (GCF2)/leucine-rich repeat (in FLII) interacting protein 1 (LRRFIP1) directly interacts with Dishevelled protein to regulate RhoA activity
physiological function
Arf6 is a critical regulator of membrane dynamics-based cellular events such as reorganization of actin cytoskeleton and membrane trafficking. Like other small GTPases, Arf6 acts as a molecular switch by cycling between GDP-bound inactive and GTP-bound active forms in cellular signaling pathways. Arf6 is activated in response to agonist stimulation of the cell interacts with its downstream effectors to regulate their intracellular location and activity
physiological function
ARL2 plays an essential role in the cellular actions of tubulin binding cofactor B (TBCD) but, rather than competing with the binding of beta-tubulin, facilitates it. The ARL2-TBCD interaction is critical for proper maintenance of microtubule densities in cells. The TBCD-ARL2-beta-tubulin trimer represents a functional complex whose activity is fundamental to microtubule dynamics. Correlation between the ability of ARL2 and ARL2 mutants to bind TBCD and to alter microtubule dynamics in a cell-based assay
physiological function
Macroautophagy (i.e. autophagy) a highly conserved intracellular process by which cytosolic components and damaged organelles are enclosed and degraded by a double membrane-bound structure, can be viewed as a continuous and dynamic membrane transport and fusion process. The GTP-bound active form of Rab13 promotes the interaction between Rab13 and growth factor receptor-bound protein 2 (Grb2). It promotes macroautophagy in vascular endothelial cells. Rab13 activates the downstream AMP-activated protein kinase (AMPK) and blocks mammalian target of rapamycin (mTOR) signaling by its functional interaction with Grb2 to regulate autophagy in HUVECs. Rab13 is a regulator of autophagy in VECs under nutrient-enriched conditions. Upregulation of the active form of Rab13 increases its interaction with Grb2, which is required to activate AMPK, leading to the inhibition of mTOR and subsequently inducing autophagy. Rab13 regulated autophagy by interacting with Grb2 in HUVECs
physiological function
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Pc-Rac1 is involved in the innate immune responses in Procambarus clarkii
physiological function
Rab proteins exist in the active GTP-bound and inactive GDP-bound conformations with the GTP/GDP exchange mediated by GTP exchange factors (GEF53) and it is the GTP-bound active form of Rab that promotes membrane trafficking upon interaction with effector proteins. Proteins of the Rab family of Ras-related small GTPases, e.g. Rab8, are MICAL regulators. The small GTPase Rab8 activates human MICAL1, small-angle X-ray scattering studies on the oligomerization state of MICAL1 (molecule interacting with casl1) and its complex with Rab8, overview. Rab8, in the active GTP-bound state, stabilizes the active MICAL1 conformation causing a specific increase of kcat
physiological function
small GTPase Rap1 plays an important role controlling intersegmental nerve b motor axon guidance during neural development. Rap1 contributes to axonal growth and guidance. Genetic interaction analyses demonstrate that the Sema-1a/PlexA-mediated repulsive guidance function is regulated positively by Rap1. The axon guidance function of Rap1 small GTPase is independent of PlexA Ras GAP activity in Drosophila melanogaster. PlexA-mediated motor axon guidance is dependent on the presence of the PlexA RasGAP domain, but not on its GAP activity toward Ras family small GTPases
physiological function
small GTPases act as molecular switches that regulate various plant responses such as disease resistance, pollen tube growth, root hair development, cell wall patterning and hormone responses. Small GTPases exhibit both GDP/GTP-binding activity and GTPase activity, and work as molecular switches by cycling between GDP-bound inactive and GTP-bound active forms. Rac/ROP family small GTPases are master regulators, controlling various signalling systems in plants such as those governing pollen tube growth, root hair development, auxin signaling, and disease resistance
physiological function
small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap2a. Rap2a can inhibit the LPS-induced phosphorylation of the NF-kappaB subunit p65 at serine 536. Rap2a is implicated in TLR-mediated responses by contributing to balanced NF-kappaB activity status in macrophages. Rap2a GTPase is involved in TLR signaling pathway to NF-kappaB. Rap2a exhibits a more potent inhibitory effect on Mal/TIRAP and TRAF6-induced NF-kappaB activation. In contrast, Rap2a fails to inhibit NF-kappaB activity induced directly by the monomer p65(RelA). Thus, Rap2a interferes in NF-kappaB activation by affecting upstream signaling events to p65(RelA)
physiological function
the putitative, Ras-like G-protein might be involved in a non-canonical signaling pathway in Plasmodium falciparum
physiological function
the small GTPase ARf6 activates PI3K in melanoma to induce a prometastatic state. ARF6 activation accelerate metastasis and increases lung colonization from circulating melanoma cells, suggesting that the prometastatic function of ARF6 extends to late steps in metastasis. ARF6 is necessary and sufficient for activation of both PI3K and AKT, and PI3K and AKT are necessary for ARF6-mediated invasion. Critical role for ARF6 in multiple steps of the metastatic cascade. ARF6 activation increases metastatic disease burden, a role for ARF6 in proliferation or survival is also possible
physiological function
the small GTPase ARf6 activates PI3K in melanoma to induce a prometastatic state. Constitutive activation of the small GTPase ARF6 (ARF6Q67L) is sufficient to accelerate metastasis in mice with BRAFV600E/Cdkn2aNULL melanoma at a similar incidence and severity to Pten loss, a major driver of PI3K activation and melanoma metastasis. ARF6 activation increases lung colonization from circulating melanoma cells, suggesting that the prometastatic function of ARF6 extends to late steps in metastasis. ARF6 is necessary and sufficient for activation of both PI3K and AKT, and PI3K and AKT are necessary for ARF6-mediated invasion. Critical role for ARF6 in multiple steps of the metastatic cascade
physiological function
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Ypt1p, a Rab family small GTPase protein, exhibits a stress-driven structural and functional switch from a GTPase to a molecular chaperone, and mediates thermo tolerance in Saccharomyces cerevisiae. The enzyme Ypt1p has another function in addition to its well-known GTPase function, which is temperature-dependent and promotes the survival and growth of cells under heat-stress. The GTPase activity of Ypt1p is not essential for the growth of yeast at elevated temperatures. Ypt1p controls an abundance of proteins involved in metabolism, protein synthesis, cellular energy generation, stress response, and DNA regulation. Ypt1p is essential for multiple steps of the yeast secretory pathway, including endoplasmic reticulum to cis-Golgi and cis- to medial-Golgi transport. Ypt1p essentially regulates fundamental cellular processes under heat-stress conditions by acting as a molecular chaperone
physiological function
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activity of Ypt7p in proteoliposome lipid mixing: Ypt7p is required for the lipid mixing of proteoliposomes lacking cardiolipin [1,3-bis-(sn-3-phosphatidyl)-sn-glycerol]. Omission of other lipids with negatively charged and/or small head groups does not cause Ypt7p dependence for lipid mixing. Disruption of cardiolipin synthase, CRD1, does not alter dependence on Rab GTPases for vacuole fusion. Lipid mixing of proteoliposomes lacking cardiolipin is completely dependent on the presence of Ypt7p. The recruitment of the HOPS, homotypic fusion and protein sorting, complex to membranes is the main function of enzyme Ypt7p. Ypt7p therefore must stimulate membrane fusion by a mechanism that is in addition to recruitment of HOPS to the membrane. Lipid mixing required soluble NSF (N-ethylmaleimide-sensitive factor)-attachment protein receptor proteins, Sec18p and Sec17p (yeast NSF and alpha-SNAP) and the HOPS (homotypic fusion and protein sorting)-class C vacuole protein sorting complex, but not the vacuolar Rab GTPase Ypt7p
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physiological function
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dual role of fission yeast Tbc1/cofactor C orchestrates microtubule homeostasis in tubulin folding and acts as a GTPase activating protein for GTPase Alp41/Arl2, Tbc1 and Alp41 directly interact, mutational analysis, overview. Tbc1 is the cofactor C involved in correct folding of alphabeta-tubulin heterodimers, critical for microtubule dynamics. The expression of GDP- or GTP-bound Alp41 shows a microtubule loss phenotype, continuous cycling between these forms seems important for its functions. Alp41 GTPase interacts with cofactor D, Alp1D, only when bound to GDP, GDP-bound Alp41 sequesters overproduced Alp1D from microtubules and rescues abnormal microtubule structures
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physiological function
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role of intrinsic expression of Cdc42 by mature B cells in their activation and function, Cdc42 expression in B cells is essential for efficient IL-2 secretion of CD4+ T cells in cognate T-B cell interaction
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physiological function
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small GTPase Rap1 regulates cell migration through regulation of small GTPase RhoA activity in response to transforming growth factor-beta1. GTP-RhoA and GTP-Rap1 levels are reciprocally regulated in a time-dependent manner following TGF-beta1 stimulation. Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states. In the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position. GTP-binding to small GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), and hydrolysis of the bound GTP is accelerated by GTPase activating proteins (GAPs). Downstream effector proteins of Rap1, including RapL, AF6, and ARAP3 transmit the activated Rap1 signals within the cells. Rap1 regulates GTPase RhoA activity, but RhoA does not regulate the Rap1 activity
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physiological function
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the small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation. The inhibitory action of Rap1b on PI3K signaling may be mediated by activation of phosphatase SHP-1. Role for Rap1b as a key suppressor of neutrophil migration and lung inflammation, which may represent an unappreciated regulatory pathway of neutrophil-related aberrant inflammatory responses. Rap1b inhibits Akt activation via CD11b outside-in signaling, Rap1b negatively regulates PI3K-Akt signaling via the phosphatase SHP-1
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physiological function
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small GTPase Rap1 regulates cell migration through regulation of small GTPase RhoA activity in response to transforming growth factor-beta1. GTP-RhoA and GTP-Rap1 levels are reciprocally regulated in a time-dependent manner following TGF-beta1 stimulation. Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states. In the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position. GTP-binding to small GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), and hydrolysis of the bound GTP is accelerated by GTPase activating proteins (GAPs), Downstream effector proteins of Rap1, including RapL, AF6, and ARAP3 transmit the activated Rap1 signals within the cells. Rap1 regulates GTPase RhoA activity, but RhoA does not regulate the Rap1 activity
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physiological function
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small GTPase Rap1 plays an important role controlling intersegmental nerve b motor axon guidance during neural development. Rap1 contributes to axonal growth and guidance. Genetic interaction analyses demonstrate that the Sema-1a/PlexA-mediated repulsive guidance function is regulated positively by Rap1. The axon guidance function of Rap1 small GTPase is independent of PlexA Ras GAP activity in Drosophila melanogaster. PlexA-mediated motor axon guidance is dependent on the presence of the PlexA RasGAP domain, but not on its GAP activity toward Ras family small GTPases
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physiological function
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Arf6 is a critical regulator of membrane dynamics-based cellular events such as reorganization of actin cytoskeleton and membrane trafficking. Like other small GTPases, Arf6 acts as a molecular switch by cycling between GDP-bound inactive and GTP-bound active forms in cellular signaling pathways. Arf6 is activated in response to agonist stimulation of the cell interacts with its downstream effectors to regulate their intracellular location and activity
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physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. The Rho GTPase FgRho4 is multifunctional and is involved in sexual development and pathogenesis. While FgRho4 is involved in cell wall integrity, and FgRho4 shows a role in nuclear division and septum formation. FgRho4 is also important for hyphal growth and conidiation. Isozyme FgRho4 plays a positive role in deoxynivalenol production. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Rho GTPase FgRho2 is multifunctional and is involved in sexual development and pathogenesis. FgRho2 is involved in cell wall integrity. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. FgRac1 interacts with FgCla4 via its PBD domain and genetically acts upstream of FgCla4 to affect hyphal growth and conidiation. Isozyme FgRac1 is important for hyphal growth and conidiation. FgRac1 negatively controls deoxynivalenol production. FgCla4 is a downstream target of FgRac1, but is dispensable for sexual development. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Isozyme FgRho3 demonstrates functions only in vegetative growth and conidiation. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. The Rho GTPase FgCdc42 is multifunctional and is involved in sexual development and pathogenesis. Isozyme FgCdc42 is important for hyphal growth and conidiation. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Isozyme FgRHO1 is essential for fungal survival. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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small GTPases act as molecular switches that regulate various plant responses such as disease resistance, pollen tube growth, root hair development, cell wall patterning and hormone responses. Small GTPases exhibit both GDP/GTP-binding activity and GTPase activity, and work as molecular switches by cycling between GDP-bound inactive and GTP-bound active forms. Rac/ROP family small GTPases are master regulators, controlling various signalling systems in plants such as those governing pollen tube growth, root hair development, auxin signaling, and disease resistance
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additional information
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activation of Rap1 by Epac1 leads to increased integrin activity and adhesion of endothelial progenitor cells, CD34+ hematopoietic progenitor cells and mesenchylmal stem cells, which show increased homing and neovascularization capabilities
additional information
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co-ordinated differential expression of a set of genes encoding small GTPases of the ARF and RAB families which takes place during key moments of fruit development and maturation
additional information
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disruption of the secretory pathway by brefeldin A does not affect autophagosome formation
additional information
each of the two Der GTP-binding domains expressed separately has an intrinsic GTPase activity, though the activity of the N-terminal GD1 domain is stronger than that of the GD2 domain
additional information
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each of the two Der GTP-binding domains expressed separately has an intrinsic GTPase activity, though the activity of the N-terminal GD1 domain is stronger than that of the GD2 domain
additional information
overexpression of any type of Rhebs (wild-type, constitutively active form, and dominant-negative form) does not affect the intact microtubule structure, and the vesicle-formed Rheb does not colocalize with the microtubule network during interphase and mitosis
additional information
Rac1 deletion in cathepsin-K+ differentiating Rac2 deficient osteoclasts has no effect on actin ring formation. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation
additional information
Rac1 deletion in cathepsin-K+ differentiating Rac2 deficient osteoclasts has no effect on actin ring formation. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation
additional information
Rac1 deletion in cathepsin-K+ differentiating Rac2 deficient osteoclasts has no effect on actin ring formation. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation
additional information
Rac1 deletion in cathepsin-K+ differentiating Rac2 deficient osteoclasts has no effect on actin ring formation. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation
additional information
real-time micrography of Toxoplasma gondii tachyzoites invading COS-7 cells overexpressing CFP-RhoA shows that this GTPase is recruited to the parasitophorous vacuole membrane at the very beginning of the invasion through the host cell membrane or from the cytosol
additional information
real-time micrography of Toxoplasma gondii tachyzoites invading COS-7 cells overexpressing CFP-RhoA shows that this GTPase is recruited to the parasitophorous vacuole membrane at the very beginning of the invasion through the host cell membrane or from the cytosol
additional information
Rho GTPase structure-function analysis, comparisons of RhoA, RhoB, and RhoC enzymes, overview. Multiple regions in RhoA/B/C cooperate to provide specificity in binding to regulators and effectors. These specific interactions are highly regulated in time and space. Visualization and analyzsis of localized GTPase activation using biosensors that allow imaging of isoform-specific, localized regulation
additional information
Rho GTPase structure-function analysis, comparisons of RhoA, RhoB, and RhoC enzymes, overview. Multiple regions in RhoA/B/C cooperate to provide specificity in binding to regulators and effectors. These specific interactions are highly regulated in time and space. Visualization and analyzsis of localized GTPase activation using biosensors that allow imaging of isoform-specific, localized regulation
additional information
Rho GTPase structure-function analysis, comparisons of RhoA, RhoB, and RhoC enzymes, overview. Multiple regions in RhoA/B/C cooperate to provide specificity in binding to regulators and effectors. These specific interactions are highly regulated in time and space. Visualization and analyzsis of localized GTPase activation using biosensors that allow imaging of isoform-specific, localized regulation
additional information
structure analysis and comparison of trypanosomal and human Arl6/BBS3 proteins, overview. Analysis of the TbArl6 active site confirms that it lacks the key glutamine that activates the nucleophile during GTP hydrolysis in other small GTPases. The trypanosomal proteins are significantly shorter at their N-termini suggesting a different method of membrane insertion compared to humans. Two surface patches may be important for protein-protein interactions
additional information
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structure analysis and comparison of trypanosomal and human Arl6/BBS3 proteins, overview. Analysis of the TbArl6 active site confirms that it lacks the key glutamine that activates the nucleophile during GTP hydrolysis in other small GTPases. The trypanosomal proteins are significantly shorter at their N-termini suggesting a different method of membrane insertion compared to humans. Two surface patches may be important for protein-protein interactions
additional information
the solvent accessibility values of all residues located in Switch I are for Phe35, Tyr39, Thr42, Val43, Phe44, and Asp45 16, 100, 55, 54, 54, and 69%, respectively
additional information
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the solvent accessibility values of all residues located in Switch I are for Phe35, Tyr39, Thr42, Val43, Phe44, and Asp45 16, 100, 55, 54, 54, and 69%, respectively
additional information
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enzyme structure-activity analysis and Ras allosteric networks, detailed overview. The allosteric networks on Ras intimately link switch I and switch II to each other and to two other functionally important regions on the opposite side of the protein. Switch I is linked to helix 5 membrane-interacting residues at the back of the molecule, where Arg161 and Arg164 make salt bridges with the interswitch loop 3 residues Asp47 and Glu49. Switch II is normally disordered and disconnected from the network. When calcium and a negatively charged ligand bind, helix 3 shifts towards helix 4, and the entire switch II becomes ordered and linked to the Ca2+-binding pocket through an extensive water-mediated network
additional information
establishment of a plant version of a Förster resonance energy transfer (FRET) probe called Ras and interacting protein chimeric unit (Raichu) that can successfully monitor activation of the rice small GTPase OsRac1 during various defence responses in cells, protocol for visualizing spatiotemporal activity of plant Rac/ ROP GTPase in living plant cells, transfection of rice protoplasts, method, detailed overview
additional information
GST-TBCD with or without ARL2 from HEK cells co-purifies with different combinations of tubulins in novel complexes. The TBCD-alpha-tubulin-beta-tubulin trimer is analyzed, overview
additional information
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GST-TBCD with or without ARL2 from HEK cells co-purifies with different combinations of tubulins in novel complexes. The TBCD-alpha-tubulin-beta-tubulin trimer is analyzed, overview
additional information
human MICAL1 is a member of a recently discovered family of multidomain proteins that couple a FAD-containing monooxygenase-like domain to typical protein interaction domains, MICAL1-Rab8 interaction analysis, quaternary structure, overview
additional information
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human MICAL1 is a member of a recently discovered family of multidomain proteins that couple a FAD-containing monooxygenase-like domain to typical protein interaction domains, MICAL1-Rab8 interaction analysis, quaternary structure, overview
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murine ectopic ARF6Q67L mutant increases Matrigel invasion of human A-2058 melanoma cells in vitro. The pan-AKT inhibitor MK2206 and the pan-Class I PI3K inhibitor GSK-0941 both abrogate ARF6Q67L-dependent Matrigel invasion, demonstrating that PI3K signaling is necessary for ARF6-mediated invasion
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murine ectopic ARF6Q67L mutant increases Matrigel invasion of human A-2058 melanoma cells in vitro. The pan-AKT inhibitor MK2206 and the pan-Class I PI3K inhibitor GSK-0941 both abrogate ARF6Q67L-dependent Matrigel invasion, demonstrating that PI3K signaling is necessary for ARF6-mediated invasion
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the enzyme has has GTP binding capacity and GTPase activity due to an EngA2 domain present in small Ras-like GTPases
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the enzyme has has GTP binding capacity and GTPase activity due to an EngA2 domain present in small Ras-like GTPases
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Ypt1p cycles between an active GTP-bound form and an inactive GDP-bound form. Native-PAGE analysis confirms that heat-shock treatment induces the reversible formation of high-molecular-weight protein complexes containing Ypt1p in vivo
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establishment of a plant version of a Förster resonance energy transfer (FRET) probe called Ras and interacting protein chimeric unit (Raichu) that can successfully monitor activation of the rice small GTPase OsRac1 during various defence responses in cells, protocol for visualizing spatiotemporal activity of plant Rac/ ROP GTPase in living plant cells, transfection of rice protoplasts, method, detailed overview
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