CGMP-dependent protein kinase

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protein kinase, cGMP-dependent, type I
Identifiers
Symbol	PRKG1 PRKGR1B, PRKG1B
HUGO	9414
Entrez	5592
OMIM	176894
RefSeq	NM_006258
UniProt	P14619
Other data
Locus	Chr. 10 q11.2

protein kinase, cGMP-dependent, type II
Identifiers
Symbol	PRKG2
HUGO	9416
Entrez	5593
OMIM	601591
RefSeq	NM_006259
UniProt	Q13237
Other data
Locus	Chr. 4 q13.1-21.1

The correct title of this article is cGMP-dependent protein kinase. The initial letter is shown capitalized due to technical restrictions.

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.

1 Genes and proteins
2 Tissue distribution
3 See also
4 External links

[edit] 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.

[edit] 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.