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Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:2.7.11.12 (
PKG
)
2,515
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
An increase in cellular levels of cyclic nucleotides activates serine/threonine-dependent kinases that lead to diverse physiological effects. Recently we reported the activation of the p38 mitogen-activated protein kinase (MAPK) pathway in neutrophils by a cGMP-dependent mechanism. In this study we demonstrated that exogenously supplied nitric oxide leads to activation of p38 MAPK in 293T fibroblasts. Phosphorylation of p38 corresponded with an increase in
ATF
-2-dependent gene expression. The effect of nitric oxide was mimicked by addition of 8-bromo-cGMP, indicating that activation of soluble guanylyl cyclase was involved. The importance of
cGMP-dependent protein kinase
in the activation of p38 MAPK by nitric oxide in 293T cells was assessed in a transfection based assay. Overexpression of
cGMP-dependent protein kinase
-1alpha caused phosphorylation of p38 in these cells and potentiated the effectiveness of cGMP. Overexpression of a catalytically inactive mutant form of this enzyme (T516A) blocked the ability of both nitric oxide and 8-bromo-cGMP to activate p38 as measured by both p38 phosphorylation and
ATF
-2 driven gene expression. Together, these data demonstrate that nitric oxide stimulates a novel pathway leading to activation of p38 MAPK that requires activation of
cGMP-dependent protein kinase
.
...
PMID:Nitric oxide activation of p38 mitogen-activated protein kinase in 293T fibroblasts requires cGMP-dependent protein kinase. 1064 46
