View source for CGMP-dependent protein kinase

{{protein
|Name=protein kinase, cGMP-dependent, type I
|caption=
|image=
|width=
|HGNCid=9414
|Symbol=PRKG1
|AltSymbols=PRKGR1B, PRKG1B
|EntrezGene=5592
|OMIM=176894
|RefSeq=NM_006258
|UniProt=P14619
|PDB=
|ECnumber=
|Chromosome=10
|Arm=q
|Band=11.2
|LocusSupplementaryData=
}}
{{protein
|Name=protein kinase, cGMP-dependent, type II
|caption=
|image=
|width=
|HGNCid=9416
|Symbol=PRKG2
|AltSymbols=
|EntrezGene=5593
|OMIM=601591
|RefSeq=NM_006259
|UniProt=Q13237
|PDB=
|ECnumber=
|Chromosome=4
|Arm=q
|Band=13.1-21.1
|LocusSupplementaryData=
}}
{{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.

==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. 

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
* (2) a ''regulatory domain'' that contains two non-identical cGMP-binding sites
* (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 that releases 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 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]], [[Clara cell]]s in [[distal]] [[airway]]s, [[intestine|intestinal mucosa]], [[pancreas|pancreatic ducts]], [[parotid]] and [[submandibular gland]]s, [[chondrocyte]]s, and several brain [[cell nucleus| cell nuclei]], but not in cardiac and vascular [[myocyte]]s.

Specifically, in smooth muscle tissue, PKG phosphorylates the ''Myosin light chain phosphatase'' which dephosphorylates the myosin light chains initiating smooth muscle relaxation.

==Role in Cancer==
On [[18 July]] [[2007]] it was discovered that cancerous colon cells stop producing PKG, which apparently limits [[beta-catenin]] thus allowing the VEGF enzyme to solicit angiogenesis.<ref>[http://www.eurekalert.org/pub_releases/2007-07/mcog-eeb071807.php Role of PKG in Angiogenesis]</ref>

== See also ==
*[[cAMP-dependent protein kinase]]

==References==
{{reflist|2}}

==External links==
*{{EC number|2.7.11.12}}
*[http://circres.ahajournals.org/cgi/content/full/93/10/907 Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System]
*{{MeshName|cGMP-Dependent+Protein+Kinases}}

{{Serine/threonine-specific protein kinases}}
[[Category:Protein kinases]]
[[Category:EC 2.7.11]]
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