Lander H M, Hajjar D P, Hempstead B L, Mirza U A, Chait B T, Campbell S, Quilliam L A
Department of Biochemistry, Cornell University Medical College.
J Biol Chem. 1997 Feb 14;272(7):4323-6. doi: 10.1074/jbc.272.7.4323.
We have identified the site of molecular interaction between nitric oxide (NO) and p21(ras) responsible for initiation of signal transduction. We found that p21(ras) was singly S-nitrosylated and localized this modification to a fragment of p21(ras) containing Cys118. A mutant form of p21(ras), in which Cys118 was changed to a serine residue and termed p21(ras)C118S, was not S-nitrosylated. NO-related species stimulated guanine nucleotide exchange on wild-type p21(ras), resulting in an active form, but not on p21(ras)C118S. Furthermore, in contrast to parental Jurkat T cells, NO-related species did not stimulate mitogen-activated protein kinase activity in cells transfected with p21(ras)C118S. These data indicate that Cys118 is a critical site of redox regulation of p21(ras), and S-nitrosylation of this residue triggers guanine nucleotide exchange and downstream signaling.
我们已经确定了一氧化氮（NO）与p21(ras)之间负责启动信号转导的分子相互作用位点。我们发现p21(ras)被单个亚硝基化，并将这种修饰定位到含有Cys118的p21(ras)片段上。一种p21(ras)的突变形式，其中Cys118被改变为丝氨酸残基，称为p21(ras)C118S，未被亚硝基化。与NO相关的物质刺激野生型p21(ras)上的鸟嘌呤核苷酸交换，产生一种活性形式，但对p21(ras)C118S则无此作用。此外，与亲本Jurkat T细胞相比，与NO相关的物质不会刺激用p21(ras)C118S转染的细胞中的丝裂原活化蛋白激酶活性。这些数据表明，Cys118是p21(ras)氧化还原调节的关键位点，该残基的亚硝基化触发鸟嘌呤核苷酸交换和下游信号传导。
