CARBOXYL METHYLATION OF RAS-RELATED PROTEINS DURING SIGNAL TRANSDUCTION IN NEUTROPHILS
CARBOXYL METHYLATION OF RAS-RELATED PROTEINS DURING SIGNAL TRANSDUCTION IN NEUTROPHILS
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DOI：
10.1126/science.8438158
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发表时间：
1993-02-12
期刊：
影响因子：
56.9
通讯作者：
STOCK, JB
中科院分区：
文献类型：
--
作者：
PHILIPS, MR;PILLINGER, MH;STOCK, JB
在人类嗜中性粒细胞，在其他类型的细胞，Ras相关的鸟苷三磷酸结合蛋白是针对他们的监管目标，在膜上的一系列翻译后修饰，包括甲酯化的羧基末端异戊二烯半胱氨酸残基。在完整的细胞和体外重建系统中，Ras相关蛋白的羧基甲基化的量增加，响应于化学引诱物N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）。鸟苷-5 '-O-（3-硫代三磷酸）激活Ras相关蛋白具有类似的作用，并诱导p22 rac 2从胞质溶胶易位到质膜。异戊二烯基半胱氨酸羧基甲基化抑制剂有效地阻断了中性粒细胞对FMLP的反应。这些发现表明受体介导的信号转导和Ras相关蛋白的羧基甲基化之间存在直接联系。
In human neutrophils, as in other cell types, Ras-related guanosine triphosphate binding proteins are directed toward their regulatory targets in membranes by a series of posttranslational modifications that include methyl esterification of a carboxyl-terminal prenylcysteine residue. In intact cells and in a reconstituted in vitro system, the amount of carboxyl methylation of Ras-related proteins increased in response to the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP). Activation of Ras-related proteins by guanosine-5'-O-(3-thiotriphosphate) had a similar effect and induced translocation of p22rac2 from cytosol to plasma membrane. Inhibitors of prenylcysteine carboxyl methylation effectively blocked neutrophil responses to FMLP. These findings suggest a direct link between receptor-mediated signal transduction and the carboxyl methylation of Ras-related proteins.