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{{protein | {{distinguish2|[[Comparison of e-book formats#Newton eBook|the .pkg eBook format]]}} | ||
|Name=protein kinase, cGMP-dependent, type I | {{infobox protein | ||
|caption= | |Name= [[PRKG1|protein kinase, cGMP-dependent, type I]] | ||
|image= | |caption= [[X-ray crystallography#Biological macromolecular crystallography|Crystallographic structure]] of the [[leucine zipper]] domain of human cGMP dependent protein kinase I beta.<ref name="pmid20826808">{{PDB|3NMD}}; {{cite journal | vauthors = Casteel DE, Smith-Nguyen EV, Sankaran B, Roh SH, Pilz RB, Kim C | title = A crystal structure of the cyclic GMP-dependent protein kinase I{beta} dimerization/docking domain reveals molecular details of isoform-specific anchoring | journal = J. Biol. Chem. | volume = 285 | issue = 43 | pages = 32684–8 | date =October 2010 | pmid = 20826808 | doi = 10.1074/jbc.C110.161430 | url = | issn = | pmc=2963381}}</ref> | ||
|width= | |image= CGMP-dependent.png | ||
|width= | |||
|HGNCid=9414 | |HGNCid=9414 | ||
|Symbol=PRKG1 | |Symbol=[[PRKG1]] | ||
|AltSymbols=PRKGR1B, PRKG1B | |AltSymbols=PRKGR1B, PRKG1B | ||
|EntrezGene=5592 | |EntrezGene=5592 | ||
|OMIM=176894 | |OMIM=176894 | ||
|RefSeq=NM_006258 | |RefSeq=NM_006258 | ||
|UniProt= | |UniProt=Q13976 | ||
|PDB= | |PDB= | ||
|ECnumber= | |ECnumber= | ||
| Line 18: | Line 19: | ||
|LocusSupplementaryData= | |LocusSupplementaryData= | ||
}} | }} | ||
{{protein | {{infobox protein | ||
|Name=protein kinase, cGMP-dependent, type II | |Name=protein kinase, cGMP-dependent, type II | ||
|caption= | |caption= | ||
| Line 39: | Line 40: | ||
{{lowercase|title=cGMP-dependent protein kinase}} | {{lowercase|title=cGMP-dependent protein kinase}} | ||
'''cGMP-dependent protein kinase''' or '''Protein Kinase G (PKG)''' is a [[serine/threonine-specific protein kinase]] that is activated by [[cyclic guanosine monophosphate|cGMP]]. It phosphorylates a number of biologically important targets and is implicated in the regulation of [[smooth muscle]] relaxation, [[platelet]] function, [[spermatozoon|sperm]] metabolism, [[cell division]] ,and [[nucleic acid]] synthesis. | '''cGMP-dependent protein kinase''' or '''Protein Kinase G (PKG)''' is a [[serine/threonine-specific protein kinase]] that is activated by [[cyclic guanosine monophosphate|cGMP]]. It [[phosphorylation|phosphorylates]] a number of biologically important targets and is implicated in the regulation of [[smooth muscle]] relaxation, [[platelet]] function, [[spermatozoon|sperm]] metabolism, [[cell division]], and [[nucleic acid]] synthesis. | ||
==Genes and proteins== | ==Genes and proteins== | ||
PKG are serine/threonine kinases that are present in a variety of [[eukaryote]]s ranging from the unicellular organism ''[[Paramecium]]'' to humans. Two PKG [[gene]]s, coding for PKG type I (PKG-I) and type II (PKG-II), have been identified in [[mammal]]s. The [[N-terminus]] of PKG-I is encoded by two alternatively spliced [[exon]]s that specify for the PKG-Iα and PKG-Iβ [[isoform]]s. PKG-Iβ is activated at ~10-fold higher cGMP concentrations than PKG-Iα. The PKG-I and PKG-II are [[homodimer]]s of two identical [[protein subunit|subunits]] (~75 kDa and ~85 kDa, respectively) and share common structural features. | PKG are serine/threonine kinases that are present in a variety of [[eukaryote]]s ranging from the unicellular organism ''[[Paramecium]]'' to humans. Two PKG [[gene]]s, coding for PKG type I (PKG-I) and type II (PKG-II), have been identified in [[mammal]]s. The [[N-terminus]] of PKG-I is encoded by two alternatively spliced [[exon]]s that specify for the PKG-Iα and PKG-Iβ [[isoform]]s. PKG-Iβ is activated at ~10-fold higher cGMP concentrations than PKG-Iα. The PKG-I and PKG-II are [[homodimer]]s of two identical [[protein subunit|subunits]] (~75 kDa and ~85 kDa, respectively) and share common structural features. | ||
Each subunit is composed of three [[structural domain|functional domains]]: | Each subunit is composed of three [[structural domain|functional domains]]: | ||
* (1) an ''N-terminal domain'' that mediates homodimerization, suppression of the kinase activity in the absence of cGMP, and interactions with other proteins including protein substrates | * (1) an ''N-terminal domain'' that mediates homodimerization, suppression of the kinase activity in the absence of cGMP, and interactions with other proteins including protein substrates | ||
| Line 50: | Line 51: | ||
* (3) a ''kinase domain'' that catalyzes the [[phosphate]] transfer from [[Adenosine triphosphate|ATP]] to the [[hydroxyl]] group of a serine/threonine [[side chain]] of the target protein | * (3) a ''kinase domain'' that catalyzes the [[phosphate]] transfer from [[Adenosine triphosphate|ATP]] to the [[hydroxyl]] group of a serine/threonine [[side chain]] of the target protein | ||
Binding of cGMP to the regulatory domain induces a conformational change | Binding of cGMP to the regulatory domain induces a conformational change which stops the inhibition of the catalytic core by the N-terminus and allows the [[phosphorylation]] of substrate proteins. Whereas PKG-I is predominantly localized in the [[cytoplasm]], PKG-II is anchored to the [[plasma membrane]] by N-terminal [[myristoylation]]. | ||
==Tissue distribution== | ==Tissue distribution== | ||
In general, PKG-I and PKG-II are expressed in different cell types. | In general, PKG-I and PKG-II are expressed in different cell types. | ||
* PKG-I has been detected at high concentrations (above 0.1 µmol/L) in all types of [[smooth muscle cell]]s (SMCs) including [[Blood vessel|vascular]] SMCs and in [[platelet]]s. Lower levels are present in vascular [[endothelium]] and [[cardiomyocyte]]s. The enzyme is also expressed in [[fibroblast]]s, certain types of [[renal]] cells and [[leukocyte]]s, and in specific regions of the [[nervous system]], for example in the [[hippocampus]], in [[cerebellum|cerebellar]] [[Purkinje cells]], and in dorsal root [[ganglia]]. [[Neuron]]s express either the PKG-Iα or the PKG-Iβ isoform, platelets predominantly Iβ, and both isoforms are present in smooth muscle. | * PKG-I has been detected at high concentrations (above 0.1 µmol/L) in all types of [[smooth muscle cell]]s (SMCs) including [[Blood vessel|vascular]] SMCs and in [[platelet]]s. Lower levels are present in vascular [[endothelium]] and [[cardiomyocyte]]s. The enzyme is also expressed in [[fibroblast]]s, certain types of [[renal]] cells and [[leukocyte]]s, and in specific regions of the [[nervous system]], for example in the [[hippocampus]], in [[cerebellum|cerebellar]] [[Purkinje cells]], and in dorsal root [[ganglia]]. [[Neuron]]s express either the PKG-Iα or the PKG-Iβ isoform, platelets predominantly Iβ, and both isoforms are present in smooth muscle. | ||
* PKG-II has been detected in renal cells, [[zona glomerulosa]] cells of the [[adrenal cortex]], [[ | * PKG-II has been detected in renal cells, [[zona glomerulosa]] cells of the [[adrenal cortex]], [[club cell]]s in [[Anatomical terms of location#Proximal and distal|distal]] [[airway]]s, [[intestine|intestinal mucosa]], [[pancreas|pancreatic ducts]], [[parotid]] and [[submandibular gland]]s, [[chondrocyte]]s, and several brain nuclei, but not in cardiac and vascular [[myocyte]]s. | ||
Specifically, in smooth muscle tissue, PKG | Specifically, in smooth muscle tissue, PKG promotes the opening of [[calcium-activated potassium channel]]s, leading to [[hyperpolarization (biology)|cell hyperpolarization]] and relaxation, and blocks [[agonist]] activity of [[phospholipase C]], reducing liberation of stored calcium ions by [[inositol triphosphate]]. | ||
==Role in | ==Role in cancer== | ||
Cancerous colon cells stop producing PKG, which apparently limits [[beta-catenin]] thus allowing the VEGF enzyme to solicit angiogenesis.<ref name="pmid18260092">{{cite journal | vauthors = Kwon IK, Schoenlein PV, Delk J, Liu K, Thangaraju M, Dulin NO, Ganapathy V, Berger FG, Browning DD | title = Expression of cyclic guanosine monophosphate-dependent protein kinase in metastatic colon carcinoma cells blocks tumor angiogenesis | journal = Cancer | volume = 112 | issue = 7 | pages = 1462–70 |date=April 2008 | pmid = 18260092 | doi = 10.1002/cncr.23334 | url = | issn = }}</ref> | |||
== See also == | == See also == | ||
| Line 66: | Line 67: | ||
==References== | ==References== | ||
{{reflist | {{reflist}} | ||
==External links== | ==External links== | ||
| Line 73: | Line 74: | ||
*{{MeshName|cGMP-Dependent+Protein+Kinases}} | *{{MeshName|cGMP-Dependent+Protein+Kinases}} | ||
{{Intracellular signaling peptides and proteins}} | |||
{{Serine/threonine-specific protein kinases}} | {{Serine/threonine-specific protein kinases}} | ||
{{Enzymes}} | |||
{{Nitric oxide signaling}} | |||
{{Portal bar|Molecular and Cellular Biology|border=no}} | |||
[[Category:Protein kinases]] | [[Category:Protein kinases]] | ||
[[Category:EC 2.7.11]] | [[Category:EC 2.7.11]] | ||
Revision as of 08:10, 11 November 2017
| protein kinase, cGMP-dependent, type I | |
|---|---|
| File:CGMP-dependent.png Crystallographic structure of the leucine zipper domain of human cGMP dependent protein kinase I beta.[1] | |
| Identifiers | |
| Symbol | PRKG1 |
| Alt. symbols | PRKGR1B, PRKG1B |
| Entrez | 5592 |
| HUGO | 9414 |
| OMIM | 176894 |
| RefSeq | NM_006258 |
| UniProt | Q13976 |
| Other data | |
| Locus | Chr. 10 q11.2 |
| protein kinase, cGMP-dependent, type II | |
|---|---|
| Identifiers | |
| Symbol | PRKG2 |
| Entrez | 5593 |
| HUGO | 9416 |
| OMIM | 601591 |
| RefSeq | NM_006259 |
| UniProt | Q13237 |
| Other data | |
| Locus | Chr. 4 q13.1-21.1 |
cGMP-dependent protein kinase or Protein Kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP. It phosphorylates a number of biologically important targets and is implicated in the regulation of smooth muscle relaxation, platelet function, sperm metabolism, cell division, and nucleic acid synthesis.
Genes and proteins
PKG are serine/threonine kinases that are present in a variety of eukaryotes ranging from the unicellular organism Paramecium to humans. Two PKG genes, coding for PKG type I (PKG-I) and type II (PKG-II), have been identified in mammals. The N-terminus of PKG-I is encoded by two alternatively spliced exons that specify for the PKG-Iα and PKG-Iβ isoforms. PKG-Iβ is activated at ~10-fold higher cGMP concentrations than PKG-Iα. The PKG-I and PKG-II are homodimers of two identical subunits (~75 kDa and ~85 kDa, respectively) and share common structural features.
Each subunit is composed of three functional domains:
- (1) an N-terminal domain that mediates homodimerization, suppression of the kinase activity in the absence of cGMP, and interactions with other proteins including protein substrates
- (2) a regulatory domain that contains two non-identical cGMP-binding sites
- (3) a kinase domain that catalyzes the phosphate transfer from ATP to the hydroxyl group of a serine/threonine side chain of the target protein
Binding of cGMP to the regulatory domain induces a conformational change which stops the inhibition of the catalytic core by the N-terminus and allows the phosphorylation of substrate proteins. Whereas PKG-I is predominantly localized in the cytoplasm, PKG-II is anchored to the plasma membrane by N-terminal myristoylation.
Tissue distribution
In general, PKG-I and PKG-II are expressed in different cell types.
- PKG-I has been detected at high concentrations (above 0.1 µmol/L) in all types of smooth muscle cells (SMCs) including vascular SMCs and in platelets. Lower levels are present in vascular endothelium and cardiomyocytes. The enzyme is also expressed in fibroblasts, certain types of renal cells and leukocytes, and in specific regions of the nervous system, for example in the hippocampus, in cerebellar Purkinje cells, and in dorsal root ganglia. Neurons express either the PKG-Iα or the PKG-Iβ isoform, platelets predominantly Iβ, and both isoforms are present in smooth muscle.
- PKG-II has been detected in renal cells, zona glomerulosa cells of the adrenal cortex, club cells in distal airways, intestinal mucosa, pancreatic ducts, parotid and submandibular glands, chondrocytes, and several brain nuclei, but not in cardiac and vascular myocytes.
Specifically, in smooth muscle tissue, PKG promotes the opening of calcium-activated potassium channels, leading to cell hyperpolarization and relaxation, and blocks agonist activity of phospholipase C, reducing liberation of stored calcium ions by inositol triphosphate.
Role in cancer
Cancerous colon cells stop producing PKG, which apparently limits beta-catenin thus allowing the VEGF enzyme to solicit angiogenesis.[2]
See also
References
- ↑ PDB: 3NMD; Casteel DE, Smith-Nguyen EV, Sankaran B, Roh SH, Pilz RB, Kim C (October 2010). "A crystal structure of the cyclic GMP-dependent protein kinase I{beta} dimerization/docking domain reveals molecular details of isoform-specific anchoring". J. Biol. Chem. 285 (43): 32684–8. doi:10.1074/jbc.C110.161430. PMC 2963381. PMID 20826808.
- ↑ Kwon IK, Schoenlein PV, Delk J, Liu K, Thangaraju M, Dulin NO, Ganapathy V, Berger FG, Browning DD (April 2008). "Expression of cyclic guanosine monophosphate-dependent protein kinase in metastatic colon carcinoma cells blocks tumor angiogenesis". Cancer. 112 (7): 1462–70. doi:10.1002/cncr.23334. PMID 18260092.
External links
- EC 2.7.11.12
- Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System
- cGMP-Dependent+Protein+Kinases at the US National Library of Medicine Medical Subject Headings (MeSH)