Nitric oxide activation of p38 mitogen-activated protein kinase in 293T fibroblasts requires cGMP-dependent protein kinase

Darren D Browning, Marisa P. McShane, Caroline Marty, Richard D. Ye

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

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-1α 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.

Original languageEnglish (US)
Pages (from-to)2811-2816
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number4
DOIs
StatePublished - Jan 28 2000
Externally publishedYes

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Cyclic GMP-Dependent Protein Kinases
p38 Mitogen-Activated Protein Kinases
Fibroblasts
Nitric Oxide
Chemical activation
Phosphorylation
Gene expression
Gene Expression
HEK293 Cells
Protein-Serine-Threonine Kinases
Cyclic Nucleotides
Guanylate Cyclase
Transfection
Threonine
Neutrophils
Serine
Assays
Phosphotransferases
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Nitric oxide activation of p38 mitogen-activated protein kinase in 293T fibroblasts requires cGMP-dependent protein kinase. / Browning, Darren D; McShane, Marisa P.; Marty, Caroline; Ye, Richard D.

In: Journal of Biological Chemistry, Vol. 275, No. 4, 28.01.2000, p. 2811-2816.

Research output: Contribution to journalArticle

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