CGMP-dependent protein kinase 1958150 191859559 2008-02-16T15:10:00Z Boghog2 2428506 added link to [[PRKG1]] in protein box {{protein |Name= [[PRKG1|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}} ==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]]