NITRIC OXIDE-STIMULATED GUANINE-NUCLEOTIDE EXCHANGE ON P21(RAS)

被引:324
|
作者
LANDER, HM
OGISTE, JS
PEARCE, SFA
LEVI, R
NOVOGRODSKY, A
机构
[1] CORNELL UNIV, COLL MED, DEPT PHARMACOL, NEW YORK, NY 10021 USA
[2] CORNELL UNIV, COLL MED, DEPT MED, DIV HEMATOL ONCOL, NEW YORK, NY 10021 USA
[3] FELSENSTEIN MED RES CTR, IL-49100 PETAH TIQWA, ISRAEL
[4] TEL AVIV UNIV, SACKLER SCH MED, IL-69978 TEL AVIV, ISRAEL
关键词
D O I
10.1074/jbc.270.13.7017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The protooncogene p21(ras), 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 p21(ras) in human T cells as evidenced by an increase in GTP-bound p21(ras). In vitro studies using pure recombinant p21(ras) demonstrate that the activation is direct and reversible. Circular dichroism analysis reveals that NO induces a profound conformational change in p21(ras) 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 p21(ras) is essential for NO-induced downstream signaling, such as NF-KB activation, and that endogenous NO can activate p21(ras) in the same cell. These studies identify p21(ras) as a target of NO in T cells and suggest that NO activates p21P(ras) by an action which mimics that of guanine nucleotide exchange factors.
引用
收藏
页码:7017 / 7020
页数:4
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