PKG are serine/threonine kinases that are present in a variety of eukaryotes ranging from the unicellular organismParamecium to humans. Two PKG genes, coding for PKG type I and type 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 and share common structural features. Each subunit is composed of three functional domains:
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
a regulatory domain that contains two non-identical cGMP-binding sites
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.
PKG-I has been detected at high concentrations in all types of smooth muscle cells 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 cerebellarPurkinje 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.
In Drosophila melanogaster the foraging gene is a polymorphic trait that underlies differences in food-seeking behaviors. The forlocus is made up of Rover and Sitter 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 considered wild-type, as fruit fly populations typically exhibit a 70:30 Rover-to-Sitter ratio. The Rover and Sitter alleles are located within the 24A3-5 region of the Drosophila melanogasterpolytene chromosome, a region which contains the PKG d2g gene. PKG expression levels account for differences in forR and forSallele 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.
