Disease relevance of PRKG2

• Because cGKII mediates the effects of heat-stable enterotoxins via the cystic fibrosis transmembrane regulator Cl(-) channel, these findings define a structural target for drug design [1].
• Herein, we review the molecular mechanism of regulation of chondrocyte hypertrophy by cGKII and the interaction between cGKII and other signaling pathways [2].

High impact information on PRKG2

• Mutant and chimeric cGK proteins generated by molecular biology techniques yielded important biochemical knowledge, such as the function of the NH(2)-terminal domains of cGKI and cGKII, the identity of the cGMP-binding sites of cGKI, and the substrate specificity of the enzymes [3].
• Recently we cloned the cDNA for a rat intestinal type II cGMP dependent protein kinase (cGK II) which is highly enriched in intestinal mucosa [4].
• Guanylin is localized to secretory epithelial cells of the gallbladder and is present in the bile, whereas GC-C, cGKII, and CFTR are confined exclusively to the apical membrane of the same epithelial cells [5].
• A non-myristoylated mutant of cGKII did not support cGMP inhibition of NHE3 [6].
• In vitro conditions were identified in which NHERF2 but not NHERF1 bound cGKII [6].

Biological context of PRKG2

• The type II cGMP-dependent protein kinase (cGK) plays a pivotal role in the regulation of intestinal fluid balance in man [7].
• The type II cGMP-dependent protein kinase is an enzyme originally isolated from the small intestine, and is thought to be involved in the regulation of intestinal ion transport and fluid secretion [8].
• By using polymerase chain reaction and Southern blotting on somatic cell hybrids, the gene encoding, the type II cGMP-dependent protein kinase was mapped to human chromosome 4q13.1-q21.1 [8].
• The amino-terminal cyclic nucleotide binding site of the type II cGMP-dependent protein kinase is essential for full cyclic nucleotide-dependent activation [1].
• To address the possibility that the distinct activation mechanisms of cGKII and cGKI result from differences in the autophosphorylation of the inhibitory domain, we investigated the effects of autophosphorylation on the kinetics of activation [9].

Anatomical context of PRKG2

• Messenger RNAs encoding the type II cGMP-dependent protein kinase were detected in small intestine, colon and prostate [8].
• Extracts from transfected COS-1 cells overexpressing cGKII stimulated Ser(19) phosphorylation more than 100-fold, but only 4-fold from cGKI overexpressing cells [10].
• The NO release in the thalamus appears to act via the type II cGMP-dependent protein kinase present at high levels in the thalamic neurons [11].
• The expression levels of three genes, G1/S-specific cyclin, type II cGMP-dependent protein kinase and hepatocyte growth factor-like protein, were significantly correlated with survival (p<0.01) [12].
• Recent study revealed that cyclic guanosine monophosphate (cGMP)-dependent protein kinase II (cGKII) coupled the stop of proliferation and the start of hypertrophic differentiation of chondrocytes [2].

Associations of PRKG2 with chemical compounds

• To examine the effect of this interaction on ligand binding and kinase activation in the type II isozyme of cGMP-dependent protein kinase (cGKII), alanine was substituted for the conserved threonine or serine. cGKII was found to require the C2 amino group of cGMP and its cognate serine or threonine hydroxyl for efficient cGMP activation [1].

Other interactions of PRKG2

• Based on sequence information from this complementary DNA, the 5'-end of the type II cGMP-dependent protein kinase was amplified from human brain messenger RNA using polymerase chain reaction [8].
• A total of four different nitrated peptides were characterized and were matched to four different proteins: synaptosomal-associated protein, actin, immunoglobulin alpha Fc receptor, and cGMP-dependent protein kinase 2 [13].
• Finally, we present evidence that the dominant negative properties of this truncation mutant are specific to cGKII when compared with cAMP-dependent protein kinase Calpha and cGKIbeta [9].
• These results suggest that Ser(19) of human PTPS may be a substrate for cGKII phosphorylation also in vivo, a modification that is essential for normal activity [10].

Analytical, diagnostic and therapeutic context of PRKG2

• Molecular cloning, cDNA structure, and chromosomal localization of the human type II cGMP-dependent protein kinase [8].

References