Disease relevance of Prkg2

• Using cultured fetal mouse tibias, an in vitro model system of endochondral ossification, we also demonstrated that CNP cannot increase the longitudinal bone growth, and chondrocytic proliferation and hypertrophy, and cartilage matrix synthesis in Prkg2(-/-) mice [1].
• The type II cGK (cGKII)-deficient mice (Prkg2(-/-) mice) develop dwarfism as a result of impaired endochondral ossification, suggesting that cGKII is important for the CNP-mediated endochondral ossification [1].
• The cGK II gene is most likely to harbour gout disease independently of hyperuricaemia by using a genome-wide scan method and case-control study [2].

Psychiatry related information on Prkg2

• In a two-bottle free choice test, cGKII-/- mice showed elevated alcohol consumption [3].

High impact information on Prkg2

• The cGKII-deficient mice also developed dwarfism that was caused by a severe defect in endochondral ossification at the growth plates [4].
• Ex vivo culture of KMI chondrocytes reproduced the differentiation impairment, which was restored by introducing the adenovirus-mediated cGKII gene [5].
• In primary cultures of renal juxtaglomerular cells (JG) established from wild-type, cGKI-/-, and cGKII-/- mice, the adenylate cyclase activator forskolin stimulated renin secretion similarly in all genotypes tested [6].
• Renal renin mRNA levels both under stimulatory (low-salt diet plus ramipril) and inhibitory (high-salt diet) conditions were not different between wild-type and cGKI-/- mice, but were significantly elevated in cGKII-/- mice under all experimental conditions [6].
• Nitric oxide and cGMP regulate gene expression in neuronal and glial cells by activating type II cGMP-dependent protein kinase [7].

Biological context of Prkg2

• However, given that Prkg2(-/-) mice differ from CNP-deficient mice (Nppc(-/-) mice) in the growth plate histology, which downstream mediator(s) of cGMP play key roles in the process is still an enigma [1].
• The second class (CGKII) of amplification products contained approximately 1.1 kb of DNA sequence between the oligonucleotide primers, and this sequence showed a much lower homology (65% identity) with the bovine and human type I cDNA sequences [8].
• The CGKII amplification product was used to screen a mouse brain cDNA library, and four overlapping cDNA clones were isolated which comprised the entire CGKII coding region [8].
• Main emphasis is put on the discussion of phenotypes observed in cGK-deficient mouse models that lack cGKI and/or cGKII globally or selectively in brain regions of interest [9].

Anatomical context of Prkg2

• Here we show that targeted expression of CNP in the growth plate chondrocytes fails to rescue the skeletal defect of Prkg2(-/-) mice [1].
• An expression vector for mouse CGKII was constructed and transfected into COS-1 cells where it directed the expression of a protein kinase which was activated by cGMP with an apparent K alpha of 300 nM cGMP [8].
• In situ hybridization revealed high levels of cGKII mRNA in cerebral cortex, thalamic nuclei, hypothalamic nuclei, and in several basal forebrain regions including medial septum, striatum and amygdala [3].
• There is also evidence suggesting that cGKII in the suprachiasmatic nucleus of the hypothalamus is involved in the regulation of circadian rhythmicity [9].

Associations of Prkg2 with chemical compounds

• Cyclic GMP (cGMP)-dependent protein kinase II (Prkg2, cGK II) was identified as a potential target of the progesterone receptor (Nr3c3) in the mouse ovary based on microarray analyses [10].
• In terms of acute responses to ethanol, cGKII-/- mice were hyposensitive to hypnotic doses of ethanol as measured by the loss of righting reflex, without an alteration in their blood alcohol elimination [3].
• Activation of cGKII by cGMP increases the surface expression of AMPARs at extrasynaptic sites [11].

Regulatory relationships of Prkg2

• CGKII induction of chondrocyte hypertrophy was suppressed by cotransfection with a phosphorylation-deficient mutant of GSK-3beta [12].

Other interactions of Prkg2

• This study provides in vivo and in vitro genetic evidence that cGKII plays a critical role in CNP-mediated endochondral ossification [1].
• The CGKII protein shows highest homology to the catalytic (66% amino acid identity) and regulatory domains (45% identity) of bovine and human CGKI [8].
• It is demonstrated that loss of Col2a1 or cGKII led to abnormal endochondral ossification and skeletal development [13].
• We found that type II cGMP-dependent protein kinase (G-kinase), which is widely expressed in the brain, mediated NO- and cGMP-induced activation of the fos promoter in cells of neuronal and glial origin; the enzyme was ineffective in regulating gene expression in fibroblast-like cells [7].
• Type II cGMP-dependent protein kinase (cGK II) has been reported to be monomeric (M(r) approximately 86,000), but recent cloning and sequencing of mouse brain cGK II cDNA revealed a leucine zipper motif near its amino terminus [14].

References