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Nitric oxide-stimulated guanine nucleotide exchange on p21ras.

Authors :
Lander HM
Ogiste JS
Pearce SF
Levi R
Novogrodsky A
Source :
The Journal of biological chemistry [J Biol Chem] 1995 Mar 31; Vol. 270 (13), pp. 7017-20.
Publication Year :
1995

Abstract

The protooncogene p21ras, a monomeric G protein family member, plays a critical role in converting extracellular signals into intracellular biochemical events. Here, we report that nitric oxide (NO) activates p21ras in human T cells as evidenced by an increase in GTP-bound p21ras. In vitro studies using pure recombinant p21ras demonstrate that the activation is direct and reversible. Circular dichroism analysis reveals that NO induces a profound conformational change in p21ras in association with GDP/GTP exchange. The mechanism of activation is due to S-nitrosylation of a critical cysteine residue which stimulates guanine nucleotide exchange. Furthermore, we demonstrate that p21ras is essential for NO-induced downstream signaling, such as NF-kappa B activation, and that endogenous NO can activate p21ras in the same cell. These studies identify p21ras as a target of the same cell. These studies identify p21ras as a target of NO in T cells and suggest that NO activates p21ras by an action which mimics that of guanine nucleotide exchange factors.

Details

Language :
English
ISSN :
0021-9258
Volume :
270
Issue :
13
Database :
MEDLINE
Journal :
The Journal of biological chemistry
Publication Type :
Academic Journal
Accession number :
7706235
Full Text :
https://doi.org/10.1074/jbc.270.13.7017