Philips M R, Pillinger M H, Staud R, Volker C, Rosenfeld M G, Weissmann G, Stock J B
Department of Medicine, New York University Medical Center, NY 10016.
Science. 1993 Feb 12;259(5097):977-80. doi: 10.1126/science.8438158.
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.
与其他细胞类型一样，在人类中性粒细胞中，Ras相关的鸟苷三磷酸结合蛋白通过一系列翻译后修饰被导向膜中的调节靶点，这些修饰包括羧基末端异戊烯基半胱氨酸残基的甲酯化。在完整细胞和重组体外系统中，Ras相关蛋白的羧基甲基化量会因趋化因子N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）而增加。鸟苷-5'-O-（3-硫代三磷酸）对Ras相关蛋白的激活具有类似作用，并诱导p22rac2从胞质溶胶转移到质膜。异戊烯基半胱氨酸羧基甲基化抑制剂有效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与Ras相关蛋白的羧基甲基化之间存在直接联系。
