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Nitric oxide-stimulated guanine nucleotide exchange on p21ras.
- 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.
- Subjects :
- Antibodies pharmacology
Carbon Monoxide pharmacology
Cell Line
GTP Phosphohydrolases metabolism
Guanosine 5'-O-(3-Thiotriphosphate) metabolism
Hemoglobins pharmacology
Humans
Kinetics
NF-kappa B metabolism
Nitric Oxide physiology
Signal Transduction
Sulfur Radioisotopes
T-Lymphocytes
Tritium
Tumor Cells, Cultured
GTP-Binding Proteins metabolism
Guanosine Diphosphate metabolism
Guanosine Triphosphate metabolism
Nitric Oxide pharmacology
Proto-Oncogene Proteins p21(ras) metabolism
Subjects
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