protein kinase, cGMP-dependent, type I
Crystallographic structure of theleucine zipper domain of human cGMP dependent protein kinase I beta.[1]
Identifiers
Symbol	PRKG1
Alt. symbols	PRKGR1B, PRKG1B
NCBI gene	5592
HGNC	9414
OMIM	176894
RefSeq	NM_006258
UniProt	Q13976
Other data
Locus	Chr. 10q11.2
Search for Structures Swiss-model Domains InterPro

cGMP-dependent protein kinase orprotein kinase G (PKG) is aserine/threonine-specific protein kinase that is activated bycGMP. Itphosphorylates a number of biologically important targets and is implicated in the regulation ofsmooth muscle relaxation,platelet function,sperm metabolism,cell division, andnucleic acid synthesis.

PKG are serine/threonine kinases that are present in a variety ofeukaryotes ranging from the unicellular organismParamecium to humans. Two PKGgenes, coding for PKG type I (PKG-I) and type II (PKG-II), have been identified inmammals. TheN-terminus of PKG-I is encoded by two alternatively splicedexons that specify for the PKG-Iα and PKG-Iβisoforms. PKG-Iβ is activated at ~10-fold higher cGMP concentrations than PKG-Iα. The PKG-I and PKG-II arehomodimers of two identicalsubunits (~75 kDa and ~85 kDa, respectively) and share common structural features.

Each subunit is composed of threefunctional domains:

• (1) anN-terminal domain that mediates homodimerization, suppression of the kinase activity in the absence of cGMP, and interactions with other proteins including protein substrates
• (2) aregulatory domain that contains two non-identical cGMP-binding sites
• (3) akinase domain that catalyzes thephosphate transfer fromATP to thehydroxyl group of a serine/threonineside 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 thephosphorylation of substrate proteins. Whereas PKG-I is predominantly localized in thecytoplasm, PKG-II is anchored to theplasma membrane by N-terminalmyristoylation.

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 ofsmooth muscle cells (SMCs) includingvascular SMCs and inplatelets. Lower levels are present in vascularendothelium andcardiomyocytes. The enzyme is also expressed infibroblasts, certain types ofrenal cells andleukocytes, and in specific regions of thenervous system, for example in thehippocampus, incerebellarPurkinje cells, and in dorsal rootganglia.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 theadrenal cortex,club cells indistalairways,intestinal mucosa,pancreatic ducts,parotid andsubmandibular glands,chondrocytes, and several brain nuclei, but not in cardiac and vascularmyocytes.

Specifically, in smooth muscle tissue, PKG promotes the opening ofcalcium-activated potassium channels, leading tocell hyperpolarization and relaxation, and blocksagonist activity ofphospholipase C, reducing liberation of stored calcium ions byinositol triphosphate.

Cancerous colon cells stop producing PKG, which apparently limitsbeta-catenin, thus allowing the VEGF enzyme to solicitangiogenesis.^[2]

InDrosophila melanogaster the foraging (for)gene is apolymorphic trait that underlies differences in food-seeking behaviors. Theforlocus is made up of Rover (for^R) and Sitter (for^S)alleles, with the Rover allele being dominant. Rover individuals typically travel greater distances when foraging for food, while Sitter individuals travel less distance to forage for food. Both Rover and Sitter phenotypes are consideredwild-type, as fruit fly populations typically exhibit a 70:30 Rover-to-Sitter ratio.^[3] The Rover and Sitter alleles are located within the 24A3-5 region of theDrosophila melanogaster polytenechromosome, a region which contains the PKG d2g gene. PKG expression levels account for differences infor^R andfor^S allele frequency and therefore behavior as Rover individuals show higher PKG expression than Sitter individuals, and the Sitter phenotype can be converted to Rover by over-expression of the dg2 gene.^[4]

• cAMP-dependent protein kinase (PKA)

• EC2.7.11.12
• Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System
• cGMP-Dependent+Protein+Kinases at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

• Genes on human chromosome 10
• Genes on human chromosome 4
• Protein kinases
• EC 2.7.11

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