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.

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...
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