Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.12 (PKG)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

cAMP- and cGMP-dependent protein kinases are homologous proteins and are predicted to exhibit very similar three-dimensional structures. Their cyclic nucleotide binding domains share a high degree of amino acid sequence identity. cAMP- and cGMP-dependent protein kinases are activated relatively specifically by cAMP and cGMP, respectively; and a single alanine-threonine difference between cAMP- and cGMP-binding domains partially accounts for this specificity. Thus, it would be expected that cAMP and cGMP mediate separate physiological effects. However, owing in part to the lack of absolute specificity of either enzyme and to the relatively high level of cAMP or cGMP in certain tissues, it is also possible that either cyclic nucleotide could cross-activate the other kinase. Increases in either cAMP or cGMP cause pig coronary artery relaxation. However, only cGMP-dependent protein kinase specific cyclic nucleotide analogues are very effective in causing relaxation, and cAMP elevation in arteries treated with isoproterenol or forskolin activates cGMP-dependent protein kinase, in addition to cAMP-dependent protein kinase. Conversely, increases in either cAMP or cGMP cause Cl- secretion in T-84 colon carcinoma cells, and the cGMP level in T-84 cells can be elevated sufficiently by bacterial enterotoxin to activate cAMP-dependent protein kinase. These results imply specific regulation of cAMP- and cGMP-dependent protein kinases by the respective cyclic nucleotides, but either cyclic nucleotide is able to cross-activate the other kinase in certain tissues.
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PMID:Cross-activation: overriding cAMP/cGMP selectivities of protein kinases in tissues. 133 68

Anoikis is an essential process in which a loss of adhesion to the substratum alters intracellular signaling pathways that lead to apoptosis. Using phosphorylation of vasodilator stimulated phosphoprotein (VASP) as an indicator of cGMP-dependent protein kinase (PKG) activity in vivo, it was found that suspension of the colon epithelial cell line (CCD841) leads to rapid and transient activation of PKG that lasted several hours. The colon carcinoma lines SW480 and SW620 do not express endogenous PKG, but exogenously expressed PKG was similarly activated upon cell suspension. To determine whether PKG has a role in apoptosis following cell suspension, poly-ADP ribose polymerase (PARP) cleavage and propidium iodide staining were measured. After 24 h in suspension it was found that approximately 50% of CCD841 cells exhibited apoptosis, whereas apoptosis was not detected in either of the colon carcinoma cell lines. Inhibition of type 1 PKG by expression of a dominant negative PKG construct (G1alphaR-GFP), or by incubation with the PKG inhibitor peptide DT-2, blocked apoptosis in suspended CCD841 cells by approximately 50%. Furthermore, expression of exogenous PKG in SW620 and SW480 cells conferred partial sensitivity anoikis. Taken together these findings indicate that PKG has an important role in the induction of apoptosis following suspension of normal colon epithelial cells, and loss of PKG expression in colon tumor cells may contribute to resistance to anoikis.
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PMID:A role for cyclic-GMP dependent protein kinase in anoikis. 1613 77

This study compared Type-1 cGMP-dependent protein kinase (PKG) expression in normal and tumor tissues and examined PKG function in tumor growth. Studies with a cDNA array revealed that PKG expression was reduced in many tumors compared to respective normal tissue. This decrease in PKG expression was confirmed using quantitative RT-PCR and western blotting of matched colon specimens from normal epithelium and tumor tissue, and also in colon derived cell lines where luciferase reporter analysis revealed that the decreased expression occurred at the transcriptional level. Using SW620 colon carcinoma cells engineered for inducible expression of PKG1beta, it was found that exogenous PKG1beta lead to decreased tumor growth and invasiveness in nude mouse xenografts.
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PMID:An anti-tumor role for cGMP-dependent protein kinase. 1625 67

It was reported earlier that Escherichia coli heat stable enterotoxin (STa), a major causative agent of secretory diarrhea, can also inhibit the proliferation of colon carcinoma cells with the involvement of cGMP mediated calcium influx. In the present study it is shown that E. coli STa inhibits cell proliferation in the colonic carcinoma cell line COLO-205 by the PKG-ERK44/42 mediated signaling pathway. This enterotoxin negatively regulates cell proliferation by downregulating the activity of ERK44/42(MAPK) and subsequently the activity of a transcription regulatory protein cMyc. The antiproliferative effect of STa was reversed by LY83583, a guanylate cyclase (GC) inhibitor and KT5823, a PKG inhibitor. Thus suggesting the involvement of cGMP dependent protein kinase (PKG) in the downregulation of ERK44/42 and subsequent inactivation of cMyc activity. Moreover, it has been shown that a specific ERK44/42 inhibitor, PD98059, also inhibits cMyc activation and cell proliferation, which further confirms the involvement of ERK44/42 in the activation of cMyc. It is also shown that E. coli STa significantly inhibits the vascular endothelial growth factor (VEGF, a potent angiogenic factor) expression in COLO-205 cells and also downregulates vascular cell adhesion molecule-1 (VCAM-1, a potent metastatic factor) expression on the COLO-205 cell surface. So it is reported for the first time that E. coli STa inhibits the proliferation of the colonic carcinoma cell line COLO-205 by the PKG-ERK44/42 mediated pathway and it may have a role against the development of colon carcinoma.
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PMID:Downregulation of human colon carcinoma cell (COLO-205) proliferation through PKG-MAP kinase mediated signaling cascade by E. coli heat stable enterotoxin (STa), a potent anti-angiogenic and anti-metastatic molecule. 1782 4