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Information on EC 2.7.11.12 - cGMP-dependent protein kinase and Organism(s) Homo sapiens and UniProt Accession Q13976
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2.7.11.12 cGMP-dependent protein kinaseIUBMB Comments
CGMP is required to activate this enzyme. The enzyme occurs as a dimer in higher eukaryotes. The C-terminal region of each polypeptide chain contains the catalytic domain that includes the ATP and protein substrate binding sites. This domain catalyses the phosphorylation by ATP to specific serine or threonine residues in protein substrates . The enzyme also has two allosteric cGMP-binding sites (sites A and B). Binding of cGMP causes a conformational change that is associated with activation of the kinase .
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Word Map
- 2.7.11.12
- cyclase
-
guanylyl
-
guanylate
-
camp-dependent
- phosphodiesterase
- endothelial
- artery
-
natriuretic
- pka
- cardiac
- nitroprusside
- 8-br-cgmp
-
contractile
- atrial
- phosphoprotein
-
myocytes
-
vasodilation
- 8-bromo-cgmp
-
l-name
-
no-induced
- sildenafil
-
vasorelaxation
-
l-type
-
cgmp-mediated
-
vasodilator-stimulated
-
patch-clamp
-
membrane-permeable
- snap
- vasp
-
cell-attached
- monophosphorothioate
- nonoate
-
cgmp-independent
- zaprinast
-
no-cgmp
-
iberiotoxin
-
atp-sensitive
-
1h-1,2,4oxadiazolo4,3-aquinoxalin-1-one
-
large-conductance
- s-nitroso-n-acetylpenicillamine
-
8-bromo-cyclic
-
cgmp-specific
- cak
- drug development
- 8-bromoguanosine
- rp-camps
-
cgmp-inhibited
-
nitrovasodilators
- medicine
- mypt1
- pharmacology
-
no-sensitive
-
oxide-cyclic
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
cgmp-dependent protein kinase, protein kinase g, cyclic gmp-dependent protein kinase, cgkii, pkg-i, cgmp kinase, prkg1, pkg ii, cgk ii, cgmp-dependent protein kinase i, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CGK
CGK 1 alpha
-
-
-
-
CGK 1 beta
-
-
-
-
CGKI-alpha
-
-
-
-
cGKI-beta
-
-
-
-
cGKII
-
-
-
-
cGMP-dependent protein kinase
Foraging protein
-
-
-
-
PKG
-
-
PKG II
protein kinase G
Type II cGMP-dependent protein kinase
CGK
-
-
-
-
cGMP-dependent protein kinase
-
-
-
-
protein kinase G
-
-
-
-
Type II cGMP-dependent protein kinase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (cGMP-dependent)
CGMP is required to activate this enzyme. The enzyme occurs as a dimer in higher eukaryotes. The C-terminal region of each polypeptide chain contains the catalytic domain that includes the ATP and protein substrate binding sites. This domain catalyses the phosphorylation by ATP to specific serine or threonine residues in protein substrates [3]. The enzyme also has two allosteric cGMP-binding sites (sites A and B). Binding of cGMP causes a conformational change that is associated with activation of the kinase [4].
CAS REGISTRY NUMBER
COMMENTARY
141588-27-4
-
141588-27-4
cGMP-dependent protein kinase
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + cysteine-riche protein 2
ADP + phosphorylated vasodilator-stimulated phosphoprotein
-
i.e. CRP2, phosphorylation by cGKI and cGKII
-
-
?
ATP + epidermal growth factor receptor
ADP + phosphorylated epidermal growth factor receptor
-
the enzyme phosphorylates epidermal growth factor receptor at threonine 669 and thereby inhibits its activation
-
-
?
ATP + HER2 protein
ADP + phosphorylated HER2 protein
-
phosphorylation at threonine 686
-
-
?
ATP + human serotonin transporter mutant I425V
ADP + phosphorylated human serotonin transporter mutant I425V
-
-
-
-
?
ATP + human serotonin transporter mutant T267A
ADP + phosphorylated human serotonin transporter mutant T267A
-
-
-
-
?
ATP + human serotonin transporter mutant T267A/I425V
ADP + phosphorylated human serotonin transporter mutant T267A/I425V
-
-
-
-
?
ATP + human serotonin transporter mutant T267D
ADP + phosphorylated human serotonin transporter mutant T267D
-
-
-
-
?
ATP + human serotonin transporter mutant T267D/I425V
ADP + phosphorylated human serotonin transporter mutant T267D/I425V
-
-
-
-
?
ATP + human serotonin transporter mutant T267E
ADP + phosphorylated human serotonin transporter mutant T267E
-
-
-
-
?
ATP + TQAKRKKSLAMA
ADP + phosphorylated TQAKRKKSLAMA
-
substrate in activity assay
-
-
?
ATP + transient receptor potential channel 6
ADP + phosphorylated transient receptor potential channel 6
-
PKG phosphorylation is reduced in transient receptor potential channel 6 mutant T69A
-
-
?
ATP + vasodilator stimulated phosphoprotein
ADP + phosphorylated vasodilator stimulated phosphoprotein
ATP + vasodilator-stimulated phosphoprotein
ADP + phosphorylated vasodilator-stimulated phosphoprotein
ATP + big potassium channel BKCa
ADP + phosphorylated big potassium channel BKCa
-
phosphorylation by cGKI leads to activation of the channel, a mechanism leading to Ca2+-dependent smooth muscle relaxation
-
-
?
ATP + big potassium channel BKCa
ADP + phosphorylated big potassium channel BKCa
-
phosphorylation by cGKI
-
-
?
ATP + DAPK2 protein
ADP + DAPK2 phosphoprotein
-
i.e death-associated protein kinase 2, phosphorylation at Ser299, Ser367 and Ser368 type I cGMP-dependent protein kinase
-
-
?
ATP + DAPK2 protein
ADP + DAPK2 phosphoprotein
-
i.e death-associated protein kinase 2, phosphorylation at Ser299, Ser367 and Ser368 type I cGMP-dependent protein kinase, recombinant wild-type and mutant FLAG-tagged DAPK2 expressed in COS-7 cells, substrate detection from microarray substrate screening, overview
-
-
?
ATP + human serotonin transporter
ADP + phosphorylated human serotonin transporter
-
i.e. hSERT, the naturally occuring hSERT mutant I425V is associated with obsessive-compulsive disorder and other neuropsychiatric disorders
-
-
?
ATP + human serotonin transporter
ADP + phosphorylated human serotonin transporter
-
i.e. hSERT, no activity with hSERT mutants T276A or T276D, active with hSERT mutant I425V
-
-
?
ATP + IRAG
ADP + phosphorylated IRAG
-
phosphorylation by cGKIbeta mediates the inhibition of inositol-1,4,5-trisphosphate-dependent Ca2+-release, a mechanism leading to smooth muscle relaxation, involved in platelet aggregation
-
-
?
ATP + IRAG
ADP + phosphorylated IRAG
-
i.e. inositol-1,4,5-trisphosphate-receptor-associated cGMP kinase substrate, phosphorylation by cGKIbeta
-
-
?
ATP + p21-activated kinase
ADP + phosphorylated p21-activated kinase
-
PKG phosphorylation of p21-activated kinase, i.e. Pak, regulates HeLa cell and human umbilical vein endothelial cell morphology and cellular remodeling, time course of Pak1 activation in vivo, overview, PKG stimulates association of vasodilator-stimulated phosphoprotein VASP with Pak
-
-
?
ATP + p21-activated kinase
ADP + phosphorylated p21-activated kinase
-
activation of the wild-type p21-activated kinase, i.e. Pak1, PKG phosphorylates wild-type and mutant K299R Pak, PKG phosphorylates especially N-terminal amino acids 174, e.g. Ser21, and does not phosphorylate a fragment encompassing amino acids 67149 and only weakly phosphorylated fragments from the central region of Pak1 encompassing amino acids 147231 and the C-terminal catalytic region, amino acids 231544, no activity with Pak1 mutant S21A, overview
-
-
?
ATP + phospholamban
ADP + phosphorylated phospholamban
-
phosphorylation leads to stimulation of the sarcoendoplasmic reticulum pump Ca2+-ATPase, i.e. SERCA
-
-
?
ATP + phospholipase Cbeta3
ADP + phosphorylated phospholipase Cbeta3
-
potentially involved in inhibition of phospholipase C activity
-
-
?
ATP + phospholipase Cbeta3
ADP + phosphorylated phospholipase Cbeta3
-
phosphorylation by cGKIbeta
-
-
?
ATP + Rac1
ADP + phosphorylated Rac-1
-
the enzyme activates the recombinant Myc-tagged small GTPase Rac1 in HEK-293 cells leading to activation of PAK1, the enzyme induces phosphorylation of p38 which activates MAPK, regulation, overview
-
-
?
ATP + Rac1
ADP + phosphorylated Rac-1
-
no activity with Rac-1 mutant T17N
-
-
?
ATP + Rho
ADP + phosphorylated rho
-
phosphorylation leads to inhibition of Rho
-
-
?
ATP + septin 3
ADP + phosphorylated septin 3
-
potentially involved in vesicle trafficking
-
-
?
ATP + septin 3
ADP + phosphorylated septin 3
-
phosphorylation by cGKIbeta
-
-
?
ATP + TPIalpha
ADP + phosphorylated TPIalpha
-
involved in desensitization of TPIalpha signalling
-
-
?
ATP + TPIalpha
ADP + phosphorylated TPIalpha
-
phosphorylation by cGKIbeta
-
-
?
ATP + TRIM39
ADP + phosphorylated TRIM39
-
phosphorylation of the tripartite motif protein 39 in the conserved phosphorylation domain by PKGI, recombinantly expresses TRIM39 substrate
-
-
?
ATP + TRIM39R
ADP + phosphorylated TRIM39R
-
PKGI interacts with TRIM39R, a Rpp21 domain-containing TRIM protein, in the kinase phosphorylation domain
-
-
?
ATP + TRIM39R
ADP + phosphorylated TRIM39R
-
phosphorylation of the endogenous putative PKGI-interactor and TRIM39 variant in the conserved phosphorylation domain by PKGI, recombinantly expresses TRIM39R substrate
-
-
?
ATP + TRPC3
ADP + phosphorylated TRPC3
-
involved in inhibition of store operated Ca2+ influx
-
-
?
ATP + vasodilator stimulated phosphoprotein
ADP + phosphorylated vasodilator stimulated phosphoprotein
-
-
-
-
?
ATP + vasodilator stimulated phosphoprotein
ADP + phosphorylated vasodilator stimulated phosphoprotein
-
phosphorylation of vasodilator stimulated phosphoprotein, i.e. VASP, induces detachment of VASP and other cytoskeletal proteins from focal adhesion, phosphorylated VASP may prevent dendritic cells from migrating towards CCl19
-
-
?
ATP + vasodilator stimulated phosphoprotein
ADP + phosphorylated vasodilator stimulated phosphoprotein
-
phosphorylation at Ser239
-
-
?
ATP + vasodilator-stimulated phosphoprotein
ADP + phosphorylated vasodilator-stimulated phosphoprotein
-
-
-
-
?
ATP + vasodilator-stimulated phosphoprotein
ADP + phosphorylated vasodilator-stimulated phosphoprotein
-
i.e. VASP, phosphorylation at Ser239 by cGKI
-
-
?
additional information
?
-
enzyme plays a crucial role in the relaxation of vascular smooth muscle by lowering the intracellular level of calcium
-
-
?
additional information
?
-
-
enzyme plays a crucial role in the relaxation of vascular smooth muscle by lowering the intracellular level of calcium
-
-
?
additional information
?
-
enzyme is involved in inhibition of platelet aggregation, relaxation of smooth muscle cells, and control of cardiocyte contractility. Pathophysiological implication of the type I cGK in cardiovascular diseases, including hypertension and atherosclerosis
-
-
?
additional information
?
-
-
enzyme is involved in inhibition of platelet aggregation, relaxation of smooth muscle cells, and control of cardiocyte contractility. Pathophysiological implication of the type I cGK in cardiovascular diseases, including hypertension and atherosclerosis
-
-
?
additional information
?
-
the enzyme is thought to be involved in the regulation of intestinal ion transport and fluid secretion
-
-
?
additional information
?
-
-
the enzyme is thought to be involved in the regulation of intestinal ion transport and fluid secretion
-
-
?
additional information
?
-
plays a pivotal role in the regulation of intestinal fluid balance in man
-
-
?
additional information
?
-
-
plays a pivotal role in the regulation of intestinal fluid balance in man
-
-
?
additional information
?
-
-
cGK is a key enzyme in the nitric oxide-cGMP and natriuretic signalling cascades, it modulates smooth muscle relaxation, platelet aggregation, renin release, intestinal secretion, learning amd memory, cGKII is involved in androsterone homeostasis, pleiotropic effets of the enzyme on diverse tissues, overview
-
-
?
additional information
?
-
-
cGMP-activated PKGIalpha inhibits thrombin receptor-mediated Ca2+ mobilization in vascular smooth muscle cells, cGMP-activated PKGIbeta causes inhibition in vitro but has nearly no effect in vivo, the thrombin receptor is activated by thrombin receptor activating peptide TRAP, or lysophosphatidic acid, or U4, overview
-
-
?
additional information
?
-
-
NO induces enzyme activity responsible for modulation/inhibition of voltage-gated CaV1 and CaV2.2, i.e. L- and N-type, Ca2+ channels in neuroblastoma cells, in cardiovascular and smooth muscle cells Ca2+ channel activity is inhibited by direct nitrosylation of the channel proteins by NO, overview
-
-
?
additional information
?
-
-
sequential activation of p38 and ERK pathways by the enzyme leading to activation of the platelet integrin alphaIIb beta3
-
-
?
additional information
?
-
-
the enzyme mediates an exocytosis pathway via glycoprotein Ib-IX, and an aggregation-dependent platelet secretion pathway important for amplifying platelet activation, in stabilizing thrombi, and in arteriosclerosis and vascular remodeling, signaling mechanism activating the enzyme, overview
-
-
?
additional information
?
-
-
the enzyme negatively regulates gene expression of thrombospondin 1, which activates the transforming growth factor-beta, at both transcriptional and posttranscriptional level inhibiting the fibrogenic potential fo high D-glucose levels, overview
-
-
?
additional information
?
-
-
the enzyme performs autophosphorylation at serines 110, 114, 117, 126, and 445 and at Thr109 in vitro and in vivo
-
-
?
additional information
?
-
-
the NO/cGMP pathway including inhibits Ca2+-dependent and turbulence-induced Rap 1 activation in human platelets mediated by cGKI in platelets and megakaryocytes
-
-
?
additional information
?
-
-
through its c-Myc-, AP-1- and PEA3-binding motifs the enzyme regulates the expression of thioredoxin and thioredoxin peroxidase-1 during hormesis in response to oxidative stress-induced apoptosis, the enzyme is involved in cell protection against apoptosis and lipid oxidation
-
-
?
additional information
?
-
-
NO and cGMP protein kinase regulate dendritic-cell migration toward the lymph-node-directing chemokine CCL19, cGMP/cGK pathway, overview
-
-
?
additional information
?
-
-
PKG Ialpha attenuates necrosis and apoptosis following ischemia/reoxygenation in adult cardiomyocyte, overview
-
-
?
additional information
?
-
-
PKG inhibits p38 MAPK activation in platelets
-
-
?
additional information
?
-
-
PKGI, in part, mediates the regulation of pulmonary cell proliferation and phenotype caused by NO and cGMP, in cells that lack PKGI such as highly passaged vascular smooth muscle cells, NO and cGMP do not regulate cell proliferation and phenotype
-
-
?
additional information
?
-
-
the enzyme is involved in development of anoikis, an essential process in which a loss of adhesion to the substratum alters intracellular signaling pathways that lead to apoptosis
-
-
?
additional information
?
-
-
transcriptional regulation by the cgMP/PKG pathway affects the amount of IL-6 expression, cGMP-induced PKG activates the IL-6 promoter involving cis-acting DNA elements and transcription factors, the activation is prevented by actinomycin D, regulation system, overview
-
-
?
additional information
?
-
-
PKG phosphorylates several substrates and interacts, by engaging its N-terminal, with numerous proteins
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + big potassium channel BKCa
ADP + phosphorylated big potassium channel BKCa
-
phosphorylation by cGKI leads to activation of the channel, a mechanism leading to Ca2+-dependent smooth muscle relaxation
-
-
?
ATP + cysteine-riche protein 2
ADP + phosphorylated vasodilator-stimulated phosphoprotein
-
i.e. CRP2, phosphorylation by cGKI and cGKII
-
-
?
ATP + DAPK2 protein
ADP + DAPK2 phosphoprotein
-
i.e death-associated protein kinase 2, phosphorylation at Ser299, Ser367 and Ser368 type I cGMP-dependent protein kinase
-
-
?
ATP + epidermal growth factor receptor
ADP + phosphorylated epidermal growth factor receptor
-
the enzyme phosphorylates epidermal growth factor receptor at threonine 669 and thereby inhibits its activation
-
-
?
ATP + HER2 protein
ADP + phosphorylated HER2 protein
-
phosphorylation at threonine 686
-
-
?
ATP + human serotonin transporter
ADP + phosphorylated human serotonin transporter
-
i.e. hSERT, the naturally occuring hSERT mutant I425V is associated with obsessive-compulsive disorder and other neuropsychiatric disorders
-
-
?
ATP + IRAG
ADP + phosphorylated IRAG
-
phosphorylation by cGKIbeta mediates the inhibition of inositol-1,4,5-trisphosphate-dependent Ca2+-release, a mechanism leading to smooth muscle relaxation, involved in platelet aggregation
-
-
?
ATP + p21-activated kinase
ADP + phosphorylated p21-activated kinase
-
PKG phosphorylation of p21-activated kinase, i.e. Pak, regulates HeLa cell and human umbilical vein endothelial cell morphology and cellular remodeling, time course of Pak1 activation in vivo, overview, PKG stimulates association of vasodilator-stimulated phosphoprotein VASP with Pak
-
-
?
ATP + phospholamban
ADP + phosphorylated phospholamban
-
phosphorylation leads to stimulation of the sarcoendoplasmic reticulum pump Ca2+-ATPase, i.e. SERCA
-
-
?
ATP + phospholipase Cbeta3
ADP + phosphorylated phospholipase Cbeta3
-
potentially involved in inhibition of phospholipase C activity
-
-
?
ATP + Rac1
ADP + phosphorylated Rac-1
-
the enzyme activates the recombinant Myc-tagged small GTPase Rac1 in HEK-293 cells leading to activation of PAK1, the enzyme induces phosphorylation of p38 which activates MAPK, regulation, overview
-
-
?
ATP + Rho
ADP + phosphorylated rho
-
phosphorylation leads to inhibition of Rho
-
-
?
ATP + septin 3
ADP + phosphorylated septin 3
-
potentially involved in vesicle trafficking
-
-
?
ATP + TPIalpha
ADP + phosphorylated TPIalpha
-
involved in desensitization of TPIalpha signalling
-
-
?
ATP + TRIM39R
ADP + phosphorylated TRIM39R
-
PKGI interacts with TRIM39R, a Rpp21 domain-containing TRIM protein, in the kinase phosphorylation domain
-
-
?
ATP + TRPC3
ADP + phosphorylated TRPC3
-
involved in inhibition of store operated Ca2+ influx
-
-
?
ATP + vasodilator stimulated phosphoprotein
ADP + phosphorylated vasodilator stimulated phosphoprotein
ATP + vasodilator-stimulated phosphoprotein
ADP + phosphorylated vasodilator-stimulated phosphoprotein
-
-
-
-
?
ATP + vasodilator stimulated phosphoprotein
ADP + phosphorylated vasodilator stimulated phosphoprotein
-
-
-
-
?
ATP + vasodilator stimulated phosphoprotein
ADP + phosphorylated vasodilator stimulated phosphoprotein
-
phosphorylation of vasodilator stimulated phosphoprotein, i.e. VASP, induces detachment of VASP and other cytoskeletal proteins from focal adhesion, phosphorylated VASP may prevent dendritic cells from migrating towards CCl19
-
-
?
additional information
?
-
enzyme plays a crucial role in the relaxation of vascular smooth muscle by lowering the intracellular level of calcium
-
-
?
additional information
?
-
-
enzyme plays a crucial role in the relaxation of vascular smooth muscle by lowering the intracellular level of calcium
-
-
?
additional information
?
-
enzyme is involved in inhibition of platelet aggregation, relaxation of smooth muscle cells, and control of cardiocyte contractility. Pathophysiological implication of the type I cGK in cardiovascular diseases, including hypertension and atherosclerosis
-
-
?
additional information
?
-
-
enzyme is involved in inhibition of platelet aggregation, relaxation of smooth muscle cells, and control of cardiocyte contractility. Pathophysiological implication of the type I cGK in cardiovascular diseases, including hypertension and atherosclerosis
-
-
?
additional information
?
-
the enzyme is thought to be involved in the regulation of intestinal ion transport and fluid secretion
-
-
?
additional information
?
-
-
the enzyme is thought to be involved in the regulation of intestinal ion transport and fluid secretion
-
-
?
additional information
?
-
plays a pivotal role in the regulation of intestinal fluid balance in man
-
-
?
additional information
?
-
-
plays a pivotal role in the regulation of intestinal fluid balance in man
-
-
?
additional information
?
-
-
cGK is a key enzyme in the nitric oxide-cGMP and natriuretic signalling cascades, it modulates smooth muscle relaxation, platelet aggregation, renin release, intestinal secretion, learning amd memory, cGKII is involved in androsterone homeostasis, pleiotropic effets of the enzyme on diverse tissues, overview
-
-
?
additional information
?
-
-
cGMP-activated PKGIalpha inhibits thrombin receptor-mediated Ca2+ mobilization in vascular smooth muscle cells, cGMP-activated PKGIbeta causes inhibition in vitro but has nearly no effect in vivo, the thrombin receptor is activated by thrombin receptor activating peptide TRAP, or lysophosphatidic acid, or U4, overview
-
-
?
additional information
?
-
-
NO induces enzyme activity responsible for modulation/inhibition of voltage-gated CaV1 and CaV2.2, i.e. L- and N-type, Ca2+ channels in neuroblastoma cells, in cardiovascular and smooth muscle cells Ca2+ channel activity is inhibited by direct nitrosylation of the channel proteins by NO, overview
-
-
?
additional information
?
-
-
sequential activation of p38 and ERK pathways by the enzyme leading to activation of the platelet integrin alphaIIb beta3
-
-
?
additional information
?
-
-
the enzyme mediates an exocytosis pathway via glycoprotein Ib-IX, and an aggregation-dependent platelet secretion pathway important for amplifying platelet activation, in stabilizing thrombi, and in arteriosclerosis and vascular remodeling, signaling mechanism activating the enzyme, overview
-
-
?
additional information
?
-
-
the enzyme negatively regulates gene expression of thrombospondin 1, which activates the transforming growth factor-beta, at both transcriptional and posttranscriptional level inhibiting the fibrogenic potential fo high D-glucose levels, overview
-
-
?
additional information
?
-
-
the enzyme performs autophosphorylation at serines 110, 114, 117, 126, and 445 and at Thr109 in vitro and in vivo
-
-
?
additional information
?
-
-
the NO/cGMP pathway including inhibits Ca2+-dependent and turbulence-induced Rap 1 activation in human platelets mediated by cGKI in platelets and megakaryocytes
-
-
?
additional information
?
-
-
through its c-Myc-, AP-1- and PEA3-binding motifs the enzyme regulates the expression of thioredoxin and thioredoxin peroxidase-1 during hormesis in response to oxidative stress-induced apoptosis, the enzyme is involved in cell protection against apoptosis and lipid oxidation
-
-
?
additional information
?
-
-
NO and cGMP protein kinase regulate dendritic-cell migration toward the lymph-node-directing chemokine CCL19, cGMP/cGK pathway, overview
-
-
?
additional information
?
-
-
PKG Ialpha attenuates necrosis and apoptosis following ischemia/reoxygenation in adult cardiomyocyte, overview
-
-
?
additional information
?
-
-
PKG inhibits p38 MAPK activation in platelets
-
-
?
additional information
?
-
-
PKGI, in part, mediates the regulation of pulmonary cell proliferation and phenotype caused by NO and cGMP, in cells that lack PKGI such as highly passaged vascular smooth muscle cells, NO and cGMP do not regulate cell proliferation and phenotype
-
-
?
additional information
?
-
-
the enzyme is involved in development of anoikis, an essential process in which a loss of adhesion to the substratum alters intracellular signaling pathways that lead to apoptosis
-
-
?
additional information
?
-
-
transcriptional regulation by the cgMP/PKG pathway affects the amount of IL-6 expression, cGMP-induced PKG activates the IL-6 promoter involving cis-acting DNA elements and transcription factors, the activation is prevented by actinomycin D, regulation system, overview
-
-
?
additional information
?
-
-
PKG phosphorylates several substrates and interacts, by engaging its N-terminal, with numerous proteins
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
required for e.g. inhibition of inositol-1,4,5-trisphosphate-dependent Ca2+-release
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
8-(4-chlorophenylthio)-beta-phenyl-1,N2-ethenoguanosine-3'5'-cyclic monophophorothioate, Rp isomer
-
-
-
D-glucose
-
high levels reduce enzyme activity in vivo leading to increased thrombospondin 1-dependent activation of transforming growth factor-beta, and increased TGF-beta-dependent expression of fibronectin and collagene type IV
KT5823
-
staurosporine analogue, inhibits in vitro by selective blockage of ATP binding
Rp-8-Br-PET-cGMPS
-
PKG-I inhibition leads to abolished induction of p38 by thrombin
Rp-8-pCPT-cGMP
-
i.e. Rp-8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate, cGKI inhibitor, reverses the NO effects
Rp-8-pCPT-cGMP
-
Rp-i.e. 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate
additional information
the R-diastereomer of the phosphorothioate analog of cGMP, Rp-cGMPS, inhibits enzyme isoform PKG I by stabilizing the inactive conformation of cyclic nucleotide-binding domain
-
additional information
-
inhibition by DT-2 fusion peptide of in vitro peptide inhibitor W45 and the membrane translocation signal sequences from HIV tyrosine aminotransferase protein, and DT-3 fusion peptide of W45 and the Drosophila antennapedia homeodomain
-
additional information
-
inhibition of PKG affects platelet secretion, platelet aggregation, and Ca2+ mobilization
-
additional information
-
PKG-I inhibition leads to abolished induction of p38 by thrombin
-
additional information
-
PKGI contains autoinhibitory subdomains in the regulatory domains and two allosteric cGMP-binding sites of isozymes alpha and beta
-
additional information
-
the enzyme is inactivated by expression of a dominant negative mutant type 1alpha PKG construct
-
additional information
-
the enzyme possesses an N-terminal autoinhibitory sequence
-
additional information
-
the Rp-isomer of 8-(4-chlorophenylthio)guanosine-3'5'-cyclic monophophorothioate does not inhibit the activity of the enzyme
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Bay412272
-
YC1 analogue, stimulates the enzyme in a NO-dependent manner, inhibition of phosphodiesterase 5
YC1
-
i.e. 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, hem-dependent activation of cGK, inhibition of phosphodiesterase 5
8-Br-PET-cGMP
-
highly specific activator of both the A and B isoforms of cGMP-dependent protein kinase I
8-pCPT-CGMP
-
i.e. 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate, activation of cGKIalpha and cGKII, specificity overview
8-pCPT-CGMP
-
i.e. i.e. 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate, cGMP analogue, membrane-permeable
cGMP
-
-
661575, 661813, 662170, 662277, 671256, 672779, 672785, 673013, 676003, 701630, 702471, 703570, 762071
cGMP
-
highly dependent on, about 10fold activation, binding and activation mechanisms for wild-type and mutant PKG-Ibeta, modeling, the enzyme elongates upon cGMP binding
cGMP
-
required by the full length enzyme for activity, the activity of the recombinant catalytic domain is independent of cGMP
cGMP
-
two allosteric binding sites in the regulatory domains in PKGI isozymes, structure and mechanism, enzyme elongation by cGMP binding ehich induces conformational changes, overview
NO
-
NO stimulates PKGI in vascular smooth umscle cells contributing to cytoskelatl kinetics and phenotype, overview
additional information
-
cGKI activity is induced by NO via increased cGMP production
-
additional information
-
cGKII is upregulated by aldosterone inducation e.g. via low salt diet, NO induces cGMP production and thus increases enzyme activity, cGK is also activates via increased cGMP level by inhibition of the phosphodiesterase 5 by sildenafil, vardenafil, and taladafil, or by inhibition of Ca2+/calmodulin-specific cGMP-dependent phosphodiesterase 1
-
additional information
-
NO activates the enzyme via increased cGMP level leading to vascular relaxation
-
additional information
-
NO, from NO donor sodium nitroprusside, induces cGMP production and thus increases enzyme activity
-
additional information
-
mechanical stress also induces the enzyme, e.g. in lung epithelial cells, umbilical vein endothelial cells, and osteoblasts
-
additional information
-
the activity of transient receptor potential channel 6 channels is markedly suppressed by PKG activation
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
cGMP binding kinetics for recombinant regulatory domains of PKGI isozymes
-
additional information
additional information
-
dissociation constants for cGMP binding by wild-type and mutant PKG-Ibeta
-
additional information
additional information
-
kinetics and dissociation constants of cGMP
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000005
all-D-YGRKKRRQRRRPPLRKKKKKH
-
Cheng-Prusoff inhibition constant derived from IC50 value
0.0000028
retro-inverso-all-D-YGRKKRRQRRRPPLRKKKKKH
-
Cheng-Prusoff inhibition constant derived from IC50 value
0.0000139
YGRKKRRQRRRPPLRKKKKKH
-
Cheng-Prusoff inhibition constant derived from IC50 value
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.005
-
recombinant catalytic domain in rat mesangial cell extract in absence of cGMP
0.011
-
recombinant catalytic domain in rat mesangial cell extract in presence of cGMP
0.02
-
recombinant tetracyclin-induced catalytic domain in rat mesangial cell extract in absence of cGMP
0.026
-
recombinant tetracyclin-induced catalytic domain in rat mesangial cell extract in presence of cGMP
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
platelets express very high levels of PKG-Ibeta isoform, not PKG-Ialpha
in normal diploid fibroblasts, the gene is constitutively expressed during cell-cycle and population doubling levels
-
high expression levels of cGKI in vascular and intestinal smooth muscle, both isozymes in cardiovascular muscle, fibromuscular stroma
additional information
-
alpha and beta isozymes of cGKI show a different tissue distribution
additional information
-
no expression of PKG in colon carcinoma cell lines SW480 and SW620
additional information
-
PKG isoforms expression level normal, benign, and malignant breast tissues from 30 patients with breast cancer and 20 women with benign breast disease using quantitative realtime RT-PCR, overview. Expression of PKGIalpha, PKGIbeta, and PKGII is reduced in malignant and benign tissues compared to normal tissue to almost the same extent
additional information
-
PKG-I expression is reduced or even lost in many primary cultured and passaged cells, e.g. vascular smooth muscle cells and endothelial cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
cyclic GMP-dependent protein kinases constitute a small family of enzymes that are encoded by two genes
malfunction
-
accumulation of poly-ubiquitinated PKG-I induced by hypoxia is not affected by the endogenous activation of PKG-I by a cGMP analogue, or by the endogenous inhibition of PKG-I activity via a cell-permeable inhibitor
metabolism
physiological function
additional information
metabolism
-
importance of the cGK-I/DAPK2 signaling pathway in regulating apoptosis, overview
metabolism
-
molecular mechanisms governing the transcriptional and posttranscriptional regulation of PKG-I expression in vascular smooth muscle cells, overview
physiological function
-
cGMP-dependent protein kinase is involved in the vasodilation of human saphenous veins
physiological function
-
cGMP-dependent protein kinase type I is an essential regulator of cellular function in blood vessels throughout the body
physiological function
-
cGMP-dependent protein kinase-I (cGK-I) induces apoptosis in various cancer cell lines, and death-associated protein kinase 2, DAPK2, is one of the targets of cGK-I in apoptosis induction. Phosphorylation of DAPK2 at Ser299 by cGKI enhances DAPK2 kinase activity, but overexpression of a phospho-mimic DAPK2 mutant, DAPK2 S299D, as well as mutant S299D/S318E, strongly induce apoptosis in human breast cancer MCF-7 cells compared with wild-type DAPK2, while a S367D/S368D mutant does not
physiological function
-
PKG-I is a serine/threonine-specific protein kinase that is activated by the NO/sGC/cGMP system. PKG-I is involved in many cell functions, such as relaxation, platelet aggregation, remodelling, hypertrophy, apoptosis, differentiation, neuronal plasticity, and erectile dysfunction. PKG-I expression is controlled by RhoA and Rac1 activities. RhoA and Rac1 have opposing effects on PKG-I expression, with RhoA suppressing and Rac1 activating its promoter. RhoA regulation of the PKG-Ialpha promoter is mediated, at least in part, through binding of KLF4 to Sp1 consensus sites in the proximal promoter, which is located within the two Sp1 sites
physiological function
-
the enzyme plays an important role in the inhibition of cell proliferation and induction of apoptosis
physiological function
-
isoform PKG II activity attenuates basic fibroblast growth factor induced proliferation and migration by inhibiting the MAPK/ERK signaling pathway in glioma cells, whereas isoform PKG I does not
physiological function
-
stimulation of enzyme activity preferentially reduces cell viability in the sphere phenotype of glioblastoma cells
additional information
-
the PKG-Ialpha isoform is more sensitive to ubiquitination compared with the PKG-Ibeta isoform
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). KGP1_HUMAN
671
0
76364
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
120000
-
recombinant PKG Ibeta mutant L17A/I24A, dimeric form at 51 nM concentration, sedimentation equilibrium analysis
140000
-
recombinant PKG Ibeta mutant L31A/I38A, dimeric form at 51 nM concentration, sedimentation equilibrium analysis
170000
-
recombinant PKG Ibeta mutants L3A/L10A, L17A, and I24A, dimeric forms, sedimentation equilibrium analysis
180000
-
recombinant wild-type PKG Ibeta, dimeric form, sedimentation equilibrium analysis
40000
-
2 * 40000, about, recombinant PKGIalpha DELTA349-670, sequence calculation, 2 * 41000, about, recombinant PKGIbeta DELTA364-685, sequence calculation
41000
-
2 * 40000, about, recombinant PKGIalpha DELTA349-670, sequence calculation, 2 * 41000, about, recombinant PKGIbeta DELTA364-685, sequence calculation
76000
-
recombinant deletion mutant DELTA1-52, monomeric form, sedimentation equilibrium analysis
86000
-
recombinant PKG Ibeta mutant L17A/I24A, monomeric form at 0.95 nM concentration, sedimentation equilibrium analysis
88000
-
recombinant PKG Ibeta mutant L31A/I38A, monomeric form at 0.95 nM concentration, sedimentation equilibrium analysis
89000
-
recombinant PKG Ibeta mutant L3A/L10A/L45A/I52A, monomeric form, sedimentation equilibrium analysis
91000
-
recombinant PKGIalpha DELTA349-670, sucrose density gradient centrifugation
92000
-
recombinant PKG Ibeta mutant L31A/I38A/L45A/I52A, monomeric form, sedimentation equilibrium analysis
96000
-
recombinant PKG Ibeta mutant L3A/L10A/L17A/I24A, monomeric form, sedimentation equilibrium analysis
98000
-
recombinant PKG Ibeta leucine zipper mutant, monomeric form, sedimentation equilibrium analysis
99000
-
recombinant PKGIbeta DELTA364-685, sucrose density gradient centrifugation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
-
structure analysis of PKG-Ibeta deletion mutant DELTA1-52, light scattering
additional information
dimer
-
2 * 40000, about, recombinant PKGIalpha DELTA349-670, sequence calculation, 2 * 41000, about, recombinant PKGIbeta DELTA364-685, sequence calculation
dimer
-
dimerization of PKG Ibeta via the N-terminal dimerization domain containing an extensive leucine zipper motif modifying enzyme activity
additional information
-
analysis of the leucine zipper motif within the N-terminal dimerization domain, overview
additional information
-
dimerization of isozymes PKGIalpha and Ibeta, each subunit contains a regulatory R domain and a catalytic C domain
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
additional information
-
the PKG-Ialpha isoform is more sensitive to ubiquitination compared with the PKG-Ibeta isoform
phosphoprotein
-
autophosphorylation of isozymes at a Thr in the catalytic domain is essential, phosphorylation sites, also for other kinases, overview
phosphoprotein
-
the enzyme performs autophosphorylation at serines 110, 114, 117, 126, and 445 and at Thr109, phosphorylation at Ser110 and Ser97 of the recombinant enzyme expressed in Sf9 insect cells, phosphorylation site mapping
phosphoprotein
-
PKG-I isoforms undergo autophosphorylation, in response to sustained activation/autophosphorylation, PKG-I might becomes ubiquitinated and degraded
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
cGMP-dependent protein kinase Ib cyclic nucleotide-binding domain, hanging drop vapor diffusion method, using 0.8 M lithium sulfate monohydrate, 0.1 M sodium acetate trihydrate, pH 4.0, 4% (v/v) polyethylene glycol 200
hanging drop vapor diffusion method, using 40% (w/v) PEG 200, 200 mM lithium sulfate, and 0.1 mM tris base/hydrochloric acid (pH 8.5) at 22°C
enzyme bound with cGMP or cAMP, vapor diffusion method, using 200 mM sodium malonate at pH 5.0, 5-10% (v/v) ethylene glycol, and 20% (w/v) PEG, or 200 mM calcium chloride, 200 mM cadmium chloride, 200 mM cobalt (II) chloride, and 20% (w/v) PEG 3350
in complex with Rab11 protein, vapor diffusion method, using 0.056 M sodium phosphate monobasic monohydrate, 1.344 M potassium phosphate dibasic (pH 8.2), and 10 mM EDTA
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C42L
the mutant shows similar temperature factors, which are consistently lower than those of wild type dimers
D412A/R415A
the mutant shows reduced activity compared to the wild type enzyme
I24A
-
site-directed mutagenesis, unaltered dimerization and molecular weight compared to the wild-type enzyme
L17A
-
site-directed mutagenesis, unaltered dimerization and molecular weight compared to the wild-type enzyme
L17A/I24A
-
site-directed mutagenesis, altered dimerization and molecular weight compared to the wild-type enzyme
L17A/I24A/L31A/I38A/L45A/I52A
-
site-directed mutagenesis, altered dimerization and molecular weight compared to the wild-type enzyme
L31A/I38A
-
site-directed mutagenesis, unaltered dimerization and molecular weight compared to the wild-type enzyme
L31A/I38A/L45A/I52A
-
site-directed mutagenesis, altered dimerization and molecular weight compared to the wild-type enzyme
L3A/L10A
-
site-directed mutagenesis, altered dimerization and molecular weight compared to the wild-type enzyme
L3A/L10A/L17A/I24A
-
site-directed mutagenesis, altered dimerization and molecular weight compared to the wild-type enzyme
L3A/L10A/L45A/I52A
-
site-directed mutagenesis, altered dimerization and molecular weight compared to the wild-type enzyme
R177A
-
the mutation in isoform PKG1alpha increases the basal activity of the enzyme
R177M
-
the mutation in isoform PKG1alpha increases the basal activity of the enzyme
R177Q
-
the mutation in isoform PKG1alpha increases PKG1alpha autophosphorylation in vitro and causes a high basal kinase activity (90-95%) in the absence of cGMP
R192Q
-
the mutation in isoform in PKG1beta increases PKG1beta autophosphorylation in vitro and causes a high basal kinase activity in the absence of cGMP
additional information
additional information
-
construction of a PKG Ibeta leucine zipper mutant, and of the deletion mutant DELTA1-52 lacking the N-terminal part, mutants show slightly altered properties, overview
additional information
-
expression of constitutively active enzyme prevents glucose stimulation of thrombospondin 1 expression and TGF-beta activity
additional information
-
the enzyme is inactivated by expression of a dominant negative mutant PKG construct
additional information
-
enzyme inhibition by a dominant negative PKG construct G1alphaR-GFP, enzyme inhibition blocks apoptosis in suspended CCD841 cells
additional information
-
expression of wild-type and mutant human serotonin transporters in HeLa cells and effects on activation through phosphorylation by PKG and cell metabolism, overview
additional information
-
overexpression of active PKGIalpha, but not of the inactive mutant K390A, increases of Akt and inhibits necrosis and apoptosis in cardiomyocytes, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
immobilized metal ion affinity column chromatography and Superdex 75 gel filtration
recombinant PKGIalpha DELTA349-670 and PKGIbeta DELTA364-685 from Sf9 insect cells by 8-aminohexylamino-cAMP affinity chromatography and gel filtration
-
recombinant wild-type and mutant PKG Ibeta from Sf9 insect cells by 8-amino-hexylamino-cAMP affinity chromatography and gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
characterization of the human gene encoding the type I alpha and type I beta cGMP-dependent protein kinase
adenoviral transfection of rat adult cardiomyocytes with the human isozyme PKGIalpha and its catalytically inactive mutant PKGIalphaK390A
-
alternate splicing of the 5' end of a pre-mRNA encoded by a single gene results in isozymes alpha and beta PKGI, expression of the constitutively active catalytic region of PKGI from a lung cDNA library, and co-expression with TRIM39R in a yeast two hybrid system
-
expressed in Escherichia coli BL21(DE3) cells
expression of GFP-tagged dominant negative mutant type 1-alpha PKG in A-549 cells and of untagged mutant in HEK-293 cells
-
expression of His-tagged cGKII in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
expression of PKGIalpha DELTA349-670 and PKGIbeta DELTA364-685 consisting of the regulatory domains in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
human PKG-Ialpha and PKG-Ibeta are generated by alternative splicing of a single gene, dissection of the human PKG-I proximal core promoter reveal the presence of regulatory regions involved in basal PKG-I transcription. Regulatory domain I corresponds to high-affinity Sp1 transcription factor recognition sites and binds Sp1 and Sp3, but not Sp2, the regulatory domain II binds USF1/2 and other transcription factors
-
placental PKG Ibeta, expression of wild-type and mutant enzymes in Escherichia coli and in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
stable expression of PKGIalpha and PKGIbeta in CHO-K1 cells, overexpression of PKGIalpha and PKGIbeta in Co403 cells by adenoviral infection, only expression of PKGIalpha after treatment with 8-bromo-cGMP leads to inhibition of thrombin receptor-mediated Ca2+ mobilization
-
stable tetracycline-inducible expression of the catalytic enzyme domain in Rattus norvegicus mesangial cells leading to suppression of glucose-induced expression of thrombospondin 1 and thus of transforming growth factor-beta activaation and the TGF-beta-dependent expression of fibronectin and collagene type IV
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
cGMP-dependent protein kinase activity is restored in vascular smooth muscle cells by transfection of primary human aortic smooth muscle cells with an expression vector coding for the catalytic domain of bovine PKG
-
cGMP-dependent protein kinase is downregulated in vessels from diabetic animals or in vascular smooth muscle cells exposed to high-glucose conditions
-
overexpression of USF1/2 increased PKG-I promoter activity RhoA and Rac1 have opposing effects on PKG-I expression, with RhoA suppressing and Rac1 activating its promoter
-
PKG-I expression is suppressed by mitogenes, e.g. platelet-derived growth factor-BB, angiotenssin II, TGF-beta and TNF-alpha. RhoA and Rac1 have opposing effects on PKG-I expression, with RhoA suppressing and Rac1 activating its promoter. RhoA regulation of the PKG-Iapha promoter is mediated, at least in part, through binding of KLF4 to Sp1 consensus sites in the proximal promoter, which is located within the two Sp1 sites, overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
downregulation of cyclic GMP-dependent protein kinase-1 alpha is linked to erectile dysfunction and diabetis mellitus
medicine
pharmacology
-
enzyme inhibitors are useful in treatment of diverse physiological dysfunctions, overview
medicine
-
gene transfer of the catalytic domain of the enzyme might provide a new strategy for treatment of diabetic renal fibrosis
medicine
-
GMP-dependent protein kinase II gene is significantly related to gout disease independent of hyperuricemia
medicine
-
PKG exerts dual functional regulation of neuronal ATP-sensitive potassium channels in a sulfonylurea receptor subunit-dependent manner, which may provide new means of therapeutic intervention for manipulating neuronal excitability and/or survival
medicine
-
all-D-YGRKKRRQRRRPPLRKKKKKH may help our understanding of how blood vessels constrict and dilate and may also aid the development of new strategies and therapeutic agents targeted to the prevention and treatment of vascular disorders
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Orstavik, S.; Natarajan, V.; Tasken, K.; Jahnsen, T.; Sandberg, M.
Characterization of the human gene encoding the type I alpha and type I beta cGMP-dependent protein kinase (PRKG1)
Genomics
42
311-318
1997
Homo sapiens (Q13976), Homo sapiens
Sandberg, M.; Natarajan, V.; Ronander, I.; Kalderon, D.; Walter, U.; Lohmann, S.M.; Jahnsen, T.
Molecular cloning and predicted full-length amino acid sequence of the type I beta isozyme of cGMP-dependent protein kinase from human placenta. Tissue distribution and developmental changes in rat
FEBS Lett.
255
321-329
1989
Homo sapiens (Q13976), Homo sapiens
Fujii, M.; Ogata, T.; Takahashi, E.; Yamada, K.; Nakabayashi, K.; Oishi, M.; Ayusawa, D.
Expression of the human cGMP-dependent protein kinase II gene is lost upon introduction of SV40 T antigen or immortalization in human cells
FEBS Lett.
375
263-267
1995
Homo sapiens (Q13237), Homo sapiens
Orstavik, S.; Solberg, R.; Tasken, K.; Nordahl, M.; Altherr, M.R.; Hansson, V.; Jahnsen, T.; Sandberg, M.
Molecular cloning, cDNA structure, and chromosomal localization of the human type II cGMP-dependent protein kinase
Biochem. Biophys. Res. Commun.
220
759-765
1996
Homo sapiens (Q13237), Homo sapiens
Witczak, O.; Orstavik, S.; Natarajan, V.; Frengen, E.; Jahnsen, T.; Sandberg, M.
Characterization of the gene encoding the human type II cGMP-dependent protein kinase
Biochem. Biophys. Res. Commun.
245
113-119
1998
Homo sapiens (Q13237), Homo sapiens
Tamura, N.; Itoh, H.; Ogawa, Y.; Nakagawa, O.; Harada, M.; Chun, T.H.; Suga, S.; Yoshimasa, T.; Nakao, K.
cDNA cloning and gene expression of human type Ialpha cGMP-dependent protein kinase
Hypertension
27
552-557
1996
Homo sapiens (Q13976), Homo sapiens
Li, Z.; Zhang, G.; Feil, R.; Han, J.; Du, X.
Sequential activation of p38 and ERK pathways by cGMP-dependent protein kinase leading to activation of the platelet integrin alphaIIb beta3
Blood
107
965-972
2006
Homo sapiens, Mus musculus
Hou, Y.; Ye, R.D.; Browning, D.D.
Activation of the small GTPase Rac1 by cGMP-dependent protein kinase
Cell. Signal.
16
1061-1069
2004
Homo sapiens
Wang, S.; Wu, X.; Lincoln, T.M.; Murphy-Ullrich, J.E.
Expression of constitutively active cGMP-dependent protein kinase prevents glucose stimulation of thrombospondin 1 expression and TGF-beta activity
Diabetes
52
2144-2150
2003
Homo sapiens
Schlossmann, J.; Hofmann, F.
cGMP-dependent protein kinases in drug discovery
Drug Discov. Today
10
627-634
2005
Homo sapiens, Mus musculus, Rattus norvegicus
Baker, D.A.; Deng, W.
Cyclic GMP-dependent protein kinases in protozoa
Front. Biosci.
10
1229-1238
2005
Aplysia californica, Bos taurus, Caenorhabditis elegans, Chlamydomonas reinhardtii, Homo sapiens, Plasmodium falciparum, Plasmodium yoelii, Tetrahymena sp., Hydra oligactis (O17474), Drosophila melanogaster (P32023), Paramecium tetraurelia (Q869J9), Paramecium tetraurelia (Q869K0), Toxoplasma gondii (Q8MMP4), Eimeria maxima (Q8MMZ5), Cryptosporidium parvum (Q8MMZ6), Eimeria tenella (Q8MMZ8), Apis mellifera (Q8SSX4)
Vaandrager, A.B.; Hogema, B.M.; Edixhoven, M.; van den Burg, C.M.; Bot, A.G.; Klatt, P.; Ruth, P.; Hofmann, F.; Van Damme, J.; Vandekerckhove, J.; de Jonge, H.R.
Autophosphorylation of cGMP-dependent protein kinase type II
J. Biol. Chem.
278
28651-28658
2003
Homo sapiens, Mus musculus, Rattus norvegicus
Richie-Jannetta, R.; Francis, S.H.; Corbin, J.D.
Dimerization of cGMP-dependent protein kinase Ibeta is mediated by an extensive amino-terminal leucine zipper motif, and dimerization modulates enzyme function
J. Biol. Chem.
278
50070-50079
2003
Homo sapiens
Andoh, T.; Chiueh, C.C.; Chock, P.B.
Cyclic GMP-dependent protein kinase regulates the expression of thioredoxin and thioredoxin peroxidase-1 during hormesis in response to oxidative stress-induced apoptosis
J. Biol. Chem.
278
885-890
2003
Homo sapiens
Li, Z.; Zhang, G.; Marjanovic, J.A.; Ruan, C.; Du, X.
A platelet secretion pathway mediated by cGMP-dependent protein kinase
J. Biol. Chem.
279
42469-42475
2004
Homo sapiens, Mus musculus
Richie-Jannetta, R.; Busch, J.L.; Higgins, K.A.; Corbin, J.D.; Francis, S.H.
Isolated regulatory domains of cGMP-dependent protein kinase Ialpha and Ibeta retain dimerization and native cGMP-binding properties, and undergo isoform-specific conformational changes
J. Biol. Chem.
281
6977-6984
2006
Homo sapiens
Christensen, E.N.; Mendelsohn, M.E.
Cyclic GMP-dependent protein kinase Ialpha inhibits thrombin receptor-mediated calcium mobilization in vascular smooth muscle cells
J. Biol. Chem.
281
8409-8416
2006
Homo sapiens
Grassi, C.; D'Ascenzo, M.; Azzena, G.B.
Modulation of CaV1 and CaV2.2 channels induced by nitric oxide via cGMP-dependent protein kinase
Neurochem. Int.
45
885-893
2004
Homo sapiens
Wall, M.E.; Francis, S.H.; Corbin, J.D.; Grimes, K.; Richie-Jannetta, R.; Kotera, J.; Macdonald, B.A.; Gibson, R.R.; Trewhella, J.
Mechanisms associated with cGMP binding and activation of cGMP-dependent protein kinase
Proc. Natl. Acad. Sci. USA
100
2380-2385
2003
Homo sapiens
Danielewski, O.; Schultess, J.; Smolenski, A.
The NO/cGMP pathway inhibits Rap 1 activation in human platelets via cGMP-dependent protein kinase I
Thromb. Haemost.
93
319-325
2005
Homo sapiens
Roberts, J.D.; Chiche, J.D.; Kolpa, E.M.; Bloch, D.B.; Bloch, K.D.
cGMP-dependent protein kinase I interacts with TRIM39R, a novel Rpp21 domain-containing TRIM protein
Am. J. Physiol. Lung Cell Mol. Physiol.
293
L903-L912
2007
Homo sapiens
Giordano, D.; Magaletti, D.M.; Clark, E.A.
Nitric oxide and cGMP protein kinase (cGK) regulate dendritic-cell migration toward the lymph-node-directing chemokine CCL19
Blood
107
1537-1545
2006
Homo sapiens
Begonja, A.J.; Geiger, J.; Rukoyatkina, N.; Rauchfuss, S.; Gambaryan, S.; Walter, U.
Thrombin stimulation of p38 MAP kinase in human platelets is mediated by ADP and thromboxane A2 and inhibited by cGMP/cGMP-dependent protein kinase
Blood
109
616-618
2007
Homo sapiens
Hou, Y.; Wong, E.; Martin, J.; Schoenlein, P.V.; Dostmann, W.R.; Browning, D.D.
A role for cyclic-GMP dependent protein kinase in anoikis
Cell. Signal.
18
882-888
2006
Homo sapiens
Waldkirch, E.S.; Uckert, S.; Langnaese, K.; Richter, K.; Jonas, U.; Wolf, G.; Andersson, K.E.; Stief, C.G.; Hedlund, P.
Immunohistochemical distribution of cyclic GMP-dependent protein kinase-1 in human prostate tissue
Eur. Urol.
52
495-501
2007
Homo sapiens
Fryer, B.H.; Wang, C.; Vedantam, S.; Zhou, G.L.; Jin, S.; Fletcher, L.; Simon, M.C.; Field, J.
cGMP-dependent protein kinase phosphorylates p21-activated kinase (Pak) 1, inhibiting Pak/Nck binding and stimulating Pak/vasodilator-stimulated phosphoprotein association
J. Biol. Chem.
281
11487-11495
2006
Homo sapiens
Das, A.; Smolenski, A.; Lohmann, S.M.; Kukreja, R.C.
Cyclic GMP-dependent protein kinase Ialpha attenuates necrosis and apoptosis following ischemia/reoxygenation in adult cardiomyocyte
J. Biol. Chem.
281
38644-38652
2006
Homo sapiens
Zhang, Y.W.; Gesmonde, J.; Ramamoorthy, S.; Rudnick, G.
Serotonin transporter phosphorylation by cGMP-dependent protein kinase is altered by a mutation associated with obsessive compulsive disorder
J. Neurosci.
27
10878-10886
2007
Homo sapiens
Broderick, K.E.; Zhang, T.; Rangaswami, H.; Zeng, Y.; Zhao, X.; Boss, G.R.; Pilz, R.B.
Guanosine 3,5-cyclic monophosphate (cGMP)/cGMP-dependent protein kinase induce interleukin-6 transcription in osteoblasts
Mol. Endocrinol.
21
1148-1162
2007
Homo sapiens, Rattus norvegicus
Chang, S.J.; Tsai, M.H.; Ko, Y.C.; Tsai, P.C.; Chen, C.J.; Lai, H.M.
The cyclic GMP-dependent protein kinase II gene associates with gout disease identified by genome-wide analysis and case-control study
Ann. Rheum. Dis.
68
1213-1219
2008
Homo sapiens
Sharma, A.K.; Zhou, G.P.; Kupferman, J.; Surks, H.K.; Christensen, E.N.; Chou, J.J.; Mendelsohn, M.E.; Rigby, A.C.
Probing the interaction between the coiled-coil leucine zipper of cGMP-dependent protein kinase Ialpha and the C-terminus of the myosin binding subunit of the myosin light chain phosphatase
J. Biol. Chem.
283
32860-32869
2008
Homo sapiens
Takahashi, S.; Lin, H.; Geshi, N.; Mori, Y.; Kawarabayashi, Y.; Takami, N.; Mori, M.X.; Honda, A.; Inoue, R.
Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6
J. Physiol.
586
4209-4223
2008
Homo sapiens, Rattus norvegicus
Waldkirch, E.; Uckert, S.; Sigl, K.; Imkamp, F.; Langnaese, K.; Richter, K.; Jonas, U.; Sohn, M.; Stief, C.; Wolf, G.; Hedlund, P.
Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue
J. Sex Med.
5
536-543
2008
Homo sapiens (Q13976), Homo sapiens
Chai, Y.; Lin, Y.F.
Dual regulation of the ATP-sensitive potassium channel by activation of cGMP-dependent protein kinase
Pflugers Arch.
456
897-915
2008
Homo sapiens
Wang, S.; Li, Y.
Expression of constitutively active cGMP-dependent protein kinase inhibits glucose-induced vascular smooth muscle cell proliferation
Am. J. Physiol. Heart Circ. Physiol.
297
H2075-H2083
2009
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
Nickl, C.K.; Raidas, S.K.; Zhao, H.; Sausbier, M.; Ruth, P.; Tegge, W.; Brayden, J.E.; Dostmann, W.R.
(D)-Amino acid analogues of DT-2 as highly selective and superior inhibitors of cGMP-dependent protein kinase Ialpha
Biochim. Biophys. Acta
1804
524-532
2010
Homo sapiens, Mus musculus, Rattus norvegicus
Goncalves, R.L.; Lugnier, C.; Keravis, T.; Lopes, M.J.; Fantini, F.A.; Schmitt, M.; Cortes, S.F.; Lemos, V.S.
The flavonoid dioclein is a selective inhibitor of cyclic nucleotide phosphodiesterase type 1 (PDE1) and a cGMP-dependent protein kinase (PKG) vasorelaxant in human vascular tissue
Eur. J. Pharmacol.
620
78-83
2009
Homo sapiens
Isshiki, K.; Matsuda, S.; Tsuji, A.; Yuasa, K.
cGMP-dependent protein kinase I promotes cell apoptosis through hyperactivation of death-associated protein kinase 2
Biochem. Biophys. Res. Commun.
422
280-284
2012
Homo sapiens
Sellak, H.; Choi, C.S.; Dey, N.B.; Lincoln, T.M.
Transcriptional and post-transcriptional regulation of cGMP-dependent protein kinase (PKG-I): pathophysiological significance
Cardiovasc. Res.
97
200-207
2013
Bos taurus, Oryctolagus cuniculus, Ovis aries, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Karami-Tehrani, F.; Fallahian, F.; Atri, M.
Expression of cGMP-dependent protein kinase, PKGIalpha, PKGIbeta, and PKGII in malignant and benign breast tumors
Tumour Biol.
33
1927-1932
2012
Homo sapiens
Qin, L.; Reger, A.S.; Guo, E.; Yang, M.P.; Zwart, P.; Casteel, D.E.; Kim, C.
Structures of cGMP-dependent protein kinase (PKG) Ialpha leucine zippers reveal an interchain disulfide bond important for dimer stability
Biochemistry
54
4419-4422
2015
Homo sapiens (Q13976)
Reger, A.S.; Yang, M.P.; Koide-Yoshida, S.; Guo, E.; Mehta, S.; Yuasa, K.; Liu, A.; Casteel, D.E.; Kim, C.
Crystal structure of the cGMP-dependent protein kinase II leucine zipper and Rab11b protein complex reveals molecular details of G-kinase-specific interactions
J. Biol. Chem.
289
25393-25403
2014
Homo sapiens (Q13237)
Campbell, J.C.; Kim, J.J.; Li, K.Y.; Huang, G.Y.; Reger, A.S.; Matsuda, S.; Sankaran, B.; Link, T.M.; Yuasa, K.; Ladbury, J.E.; Casteel, D.E.; Kim, C.
Structural basis of cyclic nucleotide selectivity in cGMP-dependent protein kinase II
J. Biol. Chem.
291
5623-5633
2016
Homo sapiens (Q13237), Homo sapiens
Zhu, M.; Yao, X.; Wu, M.; Qian, H.; Wu, Y.; Chen, Y.
Type II cGMP-dependent protein kinase directly inhibits HER2 activation of gastric cancer cells
Mol. Med. Rep.
13
1909-1913
2016
Homo sapiens
Cao, Z.H.; Tao, Y.; Sang, J.R.; Gu, Y.J.; Bian, X.J.; Chen, Y.C.
Type II, but not type I, cGMP-dependent protein kinase reverses bFGF-induced proliferation and migration of U251 human glioma cells
Mol. Med. Rep.
7
1229-1234
2013
Homo sapiens
Lan, T.; Pang, J.; Wang, Z.; Wang, Y.; Qian, H.; Chen, Y.; Wu, Y.
Type II cGMP-dependent protein kinase phosphorylates EGFR at threonine 669 and thereby inhibits its activation
Biochem. Biophys. Res. Commun.
518
14-18
2019
Homo sapiens
Campbell, J.C.; VanSchouwen, B.; Lorenz, R.; Sankaran, B.; Herberg, F.W.; Melacini, G.; Kim, C.
Crystal structure of cGMP-dependent protein kinase Ib cyclic nucleotide-binding-B domain Rp-cGMPS complex reveals an apo-like, inactive conformation
FEBS Lett.
591
221-230
2017
Homo sapiens (Q13976)
Chan, M.H.; Aminzai, S.; Hu, T.; Taran, A.; Li, S.; Kim, C.; Pilz, R.B.; Casteel, D.E.
A substitution in cGMP-dependent protein kinase 1 associated with aortic disease induces an active conformation in the absence of cGMP
J. Biol. Chem.
295
10394-10405
2020
Homo sapiens
Wilson, T.J.; Zamler, D.B.; Doherty, R.; Castro, M.G.; Lowenstein, P.R.
Reversibility of glioma stem cells phenotypes explains their complex in vitro and in vivo behavior Discovery of a novel neurosphere-specific enzyme, cGMP-dependent protein kinase 1, using the genomic landscape of human glioma stem cells as a discovery tool
Oncotarget
7
63020-63041
2016
Homo sapiens
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