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Open Access Articles- Top Results for CGMP-dependent protein kinase

cGMP-dependent protein kinase

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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.

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

  1. ^ 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. PMC 2963381. PMID 20826808. doi:10.1074/jbc.C110.161430. 
  2. ^ 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. PMID 18260092. doi:10.1002/cncr.23334. 

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