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CGMP-dependent protein kinase



protein kinase, cGMP-dependent, type I
Identifiers
Symbol PRKG1
Alt. Symbols PRKGR1B, PRKG1B
Entrez 5592
HUGO 9414
OMIM 176894
RefSeq NM_006258
UniProt P14619
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
Template:DISPLAYTITLE:cGMP-dependent protein kinase

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.

Additional recommended knowledge

Contents

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 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 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, Clara cells in distal airways, intestinal mucosa, pancreatic ducts, parotid and submandibular glands, chondrocytes, and several brain cell nuclei, but not in cardiac and vascular myocytes.

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.[1]

See also

References

  1. ^ Role of PKG in Angiogenesis
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "CGMP-dependent_protein_kinase". A list of authors is available in Wikipedia.
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