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ATP + a G protein-coupled receptor
ADP + a phosphorylated G protein-coupled receptor
ATP + alpha1-adrenergic receptor
ADP + alpha1-adrenergic receptor phosphate
GRK5 is also active with alpha1-adrenergic receptors. GRK5 activity, but not GRK2 activity, toward alpha1-adrenergic receptors can lead to transactivation of the tyrosine kinase receptor for epidermal growth factor in myocytes, cf. EC 2.7.11.15
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-
?
ATP + ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
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-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
-
desensitization of the receptor by GRK4, GRK5, and GRK6
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-
?
ATP + BLT1 receptor
ADP + phosphorylated BLT1 receptor
ATP + central M2 muscarinic receptor
ADP + phosphorylated central M2 muscarinic receptor
ATP + CXCR4 receptor
ADP + phosphorylated CXCR4 receptor
ATP + dopamine D1 receptor
ADP + phosphorylated dopamine D1 receptor
-
GRK4
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
ATP + protein p105
ADP + phosphorylated protein p105
ATP + rhodopsin
ADP + phosphorylated rhodopsin
-
light-activated rhodopsin, recombinant isoforms mGRK6-A, mGRK6-B, and mGRK-C, the latter showing highest activity
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-
?
ATP + tau protein
ADP + phosphorylated tau protein
-
-
-
?
ATP + [G-protein-coupled receptor]
ADP + [G-protein-coupled receptor]phosphate
additional information
?
-
ATP + a G protein-coupled receptor
ADP + a phosphorylated G protein-coupled receptor
-
the GRKs are important in the cardiovascular system, the major G protein-coupled receptor regulatory pathway involves phosphorylation of activated receptors by GRKs, followed by binding of arrestin proteins, which prevent receptors from activating downstream heterotrimeric G protein pathways while allowing activation of arrestin-dependent signaling pathways, general mechanisms of GRK-arrestin regulation, overview, physiological functions and potential pathophysiological roles of GRKs and arrestins in human disorders, overview
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?
ATP + a G protein-coupled receptor
ADP + a phosphorylated G protein-coupled receptor
-
cell surface localized receptors
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-
?
ATP + BLT1 receptor
ADP + phosphorylated BLT1 receptor
-
GRK6, ablation of GRK6 leads to augmented signaling by leukotriene B4 acting through the BLT1 receptor
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-
?
ATP + BLT1 receptor
ADP + phosphorylated BLT1 receptor
-
GRK6
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-
?
ATP + central M2 muscarinic receptor
ADP + phosphorylated central M2 muscarinic receptor
-
desensitization of the receptor by GRK5, GRK5 regulates pulmmonary responses by activation of the airway receptor, but does not regulate the peripheral cardiac muscarinic receptors
-
-
?
ATP + central M2 muscarinic receptor
ADP + phosphorylated central M2 muscarinic receptor
-
GRK5
-
-
?
ATP + CXCR4 receptor
ADP + phosphorylated CXCR4 receptor
-
GRK6, the pathway is important in facilitating neutrophil retention in the bone marrow
-
-
?
ATP + CXCR4 receptor
ADP + phosphorylated CXCR4 receptor
-
GRK6
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
-
-
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
-
phosphorylation has a regulatory role
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
-
regulation mechanism of GRK5, overview, regulation by phosphorylation at specific sites via distinct specific kinases, overview
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?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
-
the GPCRs possess multiple phosphorylation sites for serine/threonine kinases
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-
?
ATP + protein p105
ADP + phosphorylated protein p105
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-
-
-
?
ATP + protein p105
ADP + phosphorylated protein p105
-
recombinant GST-tagged p105, residues 497-968, substrate, GRK5 binds and phosphorylates p105, to which arrestin-2 is already C-terminally bound
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?
ATP + [G-protein-coupled receptor]
ADP + [G-protein-coupled receptor]phosphate
-
-
-
-
?
ATP + [G-protein-coupled receptor]
ADP + [G-protein-coupled receptor]phosphate
-
-
-
?
additional information
?
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
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-
?
additional information
?
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
-
-
?
additional information
?
-
G protein-coupled receptors are involved in regulating pain signaling in the context of inflammation. G protein-coupled receptor kinases modulate signaling through these receptors, GRK6 controls post-inflammatory visceral hyperalgesia, overview
-
-
?
additional information
?
-
-
G protein-coupled receptors are involved in the regulation of diverse physiological processes, mechanisms of G protein-coupled receptor desensitization, e.g. by phosphorylation or feedback inhibition, overview
-
-
?
additional information
?
-
-
GRK5 defects can cause obstructive airway diseases such as asthma
-
-
?
additional information
?
-
-
GRKs are involved in diverse physiological processes and pathologies, overview
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-
?
additional information
?
-
-
the variable C-terminal extension of GRK6 constitutes an accessorial autoregulatory domain
-
-
?
additional information
?
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-
GRK5 performs autophosphorylation
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-
?
additional information
?
-
-
structure-activity relationships of the enzyme C-terminus, overview
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-
?
additional information
?
-
-
the GRKs are specific for GPCRs and arrestins, overview
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-
?
additional information
?
-
-
arrestin-2 and GRK5, not GRK6, interact with NFkappaB1 p105 and negatively regulate lipopolysaccharide-stimulated ERK1/2 activation in macrophages, overview
-
-
?
additional information
?
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
-
-
?
additional information
?
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
-
-
?
additional information
?
-
GRK5 is important for myocardial regulation, and is up-regulated in the dysfunctional heart. But GRK5 also is a nuclear a class II histone deacetylase kinase that plays a key role in maladaptive cardiac hypertrophy apparently independent of any action directly on G protein coupled receptors, overview. Chronic Gq signaling results in the translocation of GRK5 to the nucleus, where GRK5 activity plays a role in MEF2 activation, which has implications for induction of hypertrophic gene expression. GRK5 interacts with histone deacetylase kinases in vivo
-
-
?
additional information
?
-
-
GRK6 plays a role in determining the course of inflammation and controls chronicity and severity of dextran sodium sulphate-induced colitis in mice, overview
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ATP + a G protein-coupled receptor
ADP + a phosphorylated G protein-coupled receptor
-
the GRKs are important in the cardiovascular system, the major G protein-coupled receptor regulatory pathway involves phosphorylation of activated receptors by GRKs, followed by binding of arrestin proteins, which prevent receptors from activating downstream heterotrimeric G protein pathways while allowing activation of arrestin-dependent signaling pathways, general mechanisms of GRK-arrestin regulation, overview, physiological functions and potential pathophysiological roles of GRKs and arrestins in human disorders, overview
-
-
?
ATP + ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
-
-
-
?
ATP + beta-adrenergic receptor
ADP + phosphorylated beta-adrenergic receptor
-
desensitization of the receptor by GRK4, GRK5, and GRK6
-
-
?
ATP + BLT1 receptor
ADP + phosphorylated BLT1 receptor
-
GRK6, ablation of GRK6 leads to augmented signaling by leukotriene B4 acting through the BLT1 receptor
-
-
?
ATP + central M2 muscarinic receptor
ADP + phosphorylated central M2 muscarinic receptor
-
desensitization of the receptor by GRK5, GRK5 regulates pulmmonary responses by activation of the airway receptor, but does not regulate the peripheral cardiac muscarinic receptors
-
-
?
ATP + CXCR4 receptor
ADP + phosphorylated CXCR4 receptor
-
GRK6, the pathway is important in facilitating neutrophil retention in the bone marrow
-
-
?
ATP + dopamine D1 receptor
ADP + phosphorylated dopamine D1 receptor
-
GRK4
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
ATP + protein p105
ADP + phosphorylated protein p105
-
-
-
-
?
ATP + [G-protein-coupled receptor]
ADP + [G-protein-coupled receptor]phosphate
additional information
?
-
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
-
phosphorylation has a regulatory role
-
-
?
ATP + G protein-coupled receptor
ADP + phosphorylated G protein-coupled receptor
-
regulation mechanism of GRK5, overview, regulation by phosphorylation at specific sites via distinct specific kinases, overview
-
-
?
ATP + [G-protein-coupled receptor]
ADP + [G-protein-coupled receptor]phosphate
-
-
-
-
?
ATP + [G-protein-coupled receptor]
ADP + [G-protein-coupled receptor]phosphate
-
-
-
?
additional information
?
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
-
-
?
additional information
?
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
-
-
?
additional information
?
-
G protein-coupled receptors are involved in regulating pain signaling in the context of inflammation. G protein-coupled receptor kinases modulate signaling through these receptors, GRK6 controls post-inflammatory visceral hyperalgesia, overview
-
-
?
additional information
?
-
-
G protein-coupled receptors are involved in the regulation of diverse physiological processes, mechanisms of G protein-coupled receptor desensitization, e.g. by phosphorylation or feedback inhibition, overview
-
-
?
additional information
?
-
-
GRK5 defects can cause obstructive airway diseases such as asthma
-
-
?
additional information
?
-
-
GRKs are involved in diverse physiological processes and pathologies, overview
-
-
?
additional information
?
-
-
the variable C-terminal extension of GRK6 constitutes an accessorial autoregulatory domain
-
-
?
additional information
?
-
-
arrestin-2 and GRK5, not GRK6, interact with NFkappaB1 p105 and negatively regulate lipopolysaccharide-stimulated ERK1/2 activation in macrophages, overview
-
-
?
additional information
?
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
-
-
?
additional information
?
-
G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview
-
-
?
additional information
?
-
GRK5 is important for myocardial regulation, and is up-regulated in the dysfunctional heart. But GRK5 also is a nuclear a class II histone deacetylase kinase that plays a key role in maladaptive cardiac hypertrophy apparently independent of any action directly on G protein coupled receptors, overview. Chronic Gq signaling results in the translocation of GRK5 to the nucleus, where GRK5 activity plays a role in MEF2 activation, which has implications for induction of hypertrophic gene expression. GRK5 interacts with histone deacetylase kinases in vivo
-
-
?
additional information
?
-
-
GRK6 plays a role in determining the course of inflammation and controls chronicity and severity of dextran sodium sulphate-induced colitis in mice, overview
-
-
?
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additional information
capsaicin-induced referred hyperalgesia post-colitis is increased in GRK6-deficient mice compared to wild-type mice. However, referred hyperalgesia post-colitis is not affected by ablation of GRK6. GRK6 overexpression inhibits the in vitro sensitization of the capsaicin receptor TRPVI by interleukin 1beta, overview
additional information
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construction of GRK5 deletion mutant mice
additional information
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construction of isozymes mGRK6-A, mGRK6-B, mGRK-C, and mGRK-D by alternative splicing, recombinant isoforms mGRK6-A, mGRK6-B, and mGRK-C are membrane-associated, recombinant isoform mGRK6-D is inactive and located in the nucleus, structure-activity relationships of the enzyme C-terminus, overview
additional information
-
construction of transgenic tissue specific or knockout mice
additional information
-
phenotypes of several GRK and arrestin knockout mice mutants and of transgenic mice overexpressing GRK4 or GRK5, overview
additional information
-
GRK short hairpin RNA knockdown, GRK5 knockout results in altered central and lung M2 muscarinic receptor regulation, with normal heart M2 receptor regulation, while GRK4 knockout does not result in an altered phenotype, GRK6 knockout leads to altered central dopamine receptor regulation deficient lymphocyte chemotaxis, increased acute inflammation and neutrophil chemotaxis, positive correlation between certain GRK4 polymorphisms, or haplotypes, and hypertensive disease, knockout mice phenotypes, detailed overview
additional information
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GRK5 knockdown results in enhanced IkappaB kinase-mediated p105 phosphorylation and degradation, and correlates well with an enhanced LPS-stimulated ERK1/2 phosphorylation
additional information
cardiac GRK5 overexpression augments hypertrophy in vivo, pressure overload causes GRK5 nuclear accumulation in vivo, overview
additional information
-
severity of colitis is increased in GRK6-deficient and GRK6+/- mice and is accompanied by increased keratinocyte-derived chemokine levels and increased granulocyte infiltration, the chemotactic response of GRK6-/- granulocytes to supernatants of colon cultures is enhanced, phenotype, overview
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Walker, J.K.; Gainetdinov, R.R.; Feldman, D.S.; McFawn, P.K.; Caron, M.G.; Lefkowitz, R.J.; Premont, R.T.; Fisher, J.T.
G protein-coupled receptor kinase 5 regulates airway responses induced by muscarinic receptor activation
Am. J. Physiol.
286
L312-319
2004
Mus musculus
brenda
Penela, P.; Ribas, C.; Mayor, F.
Mechanisms of regulation of the expression and function of G protein-coupled receptor kinases
Cell. Signal.
15
973-981
2003
Homo sapiens, Mus musculus
brenda
Vatter, P.; Stoesser, C.; Samel, I.; Gierschik, P.; Moepps, B.
The variable C-terminal extension of G-protein-coupled receptor kinase 6 constitutes an accessorial autoregulatory domain
FEBS J.
272
6039-6051
2005
Mus musculus
brenda
Kohout, T.A.; Lefkowitz, R.J.
Regulation of G protein-coupled receptor kinases and arrestins during receptor desensitization
Mol. Pharmacol.
63
9-18
2003
Mus musculus
brenda
Premont, R.T.; Gainetdinov, R.R.
Physiological roles of G protein-coupled receptor kinases and arrestins
Annu. Rev. Physiol.
69
511-534
2007
Homo sapiens, Mus musculus
brenda
Parameswaran, N.; Pao, C.S.; Leonhard, K.S.; Kang, D.S.; Kratz, M.; Ley, S.C.; Benovic, J.L.
Arrestin-2 and G protein-coupled receptor kinase 5 interact with NFkappaB1 p105 and negatively regulate lipopolysaccharide-stimulated ERK1/2 activation in macrophages
J. Biol. Chem.
281
34159-34170
2006
Mus musculus
brenda
Cohn, H.I.; Harris, D.M.; Pesant, S.; Pfeiffer, M.; Zhou, R.H.; Koch, W.J.; Dorn, G.W.; Eckhart, A.D.
Inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances alpha1D-adrenergic receptor constriction
Am. J. Physiol. Heart Circ. Physiol.
295
H1695-H1704
2008
Mus musculus, Mus musculus (Q99MK8)
brenda
Eijkelkamp, N.; Heijnen, C.J.; Elsenbruch, S.; Holtmann, G.; Schedlowski, M.; Kavelaars, A.
G protein-coupled receptor kinase 6 controls post-inflammatory visceral hyperalgesia
Brain Behav. Immun.
23
18-26
2008
Mus musculus (O70293)
brenda
Eijkelkamp, N.; Heijnen, C.J.; Lucas, A.; Premont, R.T.; Elsenbruch, S.; Schedlowski, M.; Kavelaars, A.
G protein-coupled receptor kinase 6 controls chronicity and severity of dextran sodium sulphate-induced colitis in mice
Gut
56
847-854
2007
Mus musculus
brenda
Loniewski, K.; Shi, Y.; Pestka, J.; Parameswaran, N.
Toll-like receptors differentially regulate GPCR kinases and arrestins in primary macrophages
Mol. Immunol.
45
2312-2322
2008
Mus musculus (O70293), Mus musculus (Q8VEB1), Mus musculus C57BL/6 (O70293), Mus musculus C57BL/6 (Q8VEB1)
brenda
Martini, J.S.; Raake, P.; Vinge, L.E.; DeGeorge, B.; Chuprun, J.K.; Harris, D.M.; Gao, E.; Eckhart, A.D.; Pitcher, J.A.; Koch, W.J.
Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes
Proc. Natl. Acad. Sci. USA
105
12457-12462
2008
Mus musculus (Q8VEB1)
brenda
Packiriswamy, N.; Steury, M.; McCabe, I.C.; Fitzgerald, S.D.; Parameswaran, N.
Bacterial dose-dependent role of G protein-coupled receptor kinase 5 in Escherichia coli-induced pneumonia
Infect. Immun.
84
1633-1641
2016
Mus musculus (Q8VEB1)
brenda
Zhao, J.; Li, X.; Chen, X.; Cai, Y.; Wang, Y.; Sun, W.; Mai, H.; Yang, J.; Fan, W.; Tang, P.; Ou, M.; Zhang, Y.; Huang, X.; Zhao, B.; Cui, L.
GRK5 influences the phosphorylation of tau via GSK3beta and contributes to Alzheimer's disease
J. Cell. Physiol.
234
10411-10420
2019
Mus musculus (Q8VEB1), Mus musculus
brenda