Nitric oxide-stimulated guanine nucleotide exchange on p21ras. Academic Article uri icon

Overview

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.

publication date

  • March 31, 1995

Research

keywords

  • GTP-Binding Proteins
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • Nitric Oxide
  • Proto-Oncogene Proteins p21(ras)

Identity

Scopus Document Identifier

  • 0028940301

Digital Object Identifier (DOI)

  • 10.1074/jbc.270.13.7017

PubMed ID

  • 7706235

Additional Document Info

volume

  • 270

issue

  • 13