Details

Autor(en) / Beteiligte

• Lander, Harry M.
• Ogiste, Jason S.
• Pearce, S. Frieda A.
• Levi, Roberto
• Novogrodsky, Abraham

Titel

Nitric Oxide-stimulated Guanine Nucleotide Exchange on p21ras(∗)

Ist Teil von

• The Journal of biological chemistry, 1995-03, Vol.270 (13), p.7017-7020

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1995

Quelle

MEDLINE

Beschreibungen/Notizen

• 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-κB activation, and that endogenous NO can activate p21ras in 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.