Burnham M R, Harte M T, Bouton A H
Department of Microbiology and Cancer Center, University of Virginia Health Science Center, Charlottesville 22908, USA.
Mol Carcinog. 1999 Sep;26(1):20-31. doi: 10.1002/(sici)1098-2744(199909)26:1<20::aid-mc3>3.0.co;2-m.
Several lines of evidence indicate that the adapter molecule p130CAS (crk-associated substrate (CAS)) is required for src-mediated cellular transformation. CAS has been shown to be heavily tyrosine-phosphorylated in src-transformed cells, and genetic variants of src that are deficient in CAS binding are also unable to mediate cellular transformation. In this report, we investigated whether CAS phosphorylation and/or its association with src are required elements of the transformation process. Expression of the carboxy-terminal src binding domain of CAS in Rat 1 fibroblasts expressing a temperature-sensitive allele of v-src inhibited the formation of src-CAS complexes and also inhibited tyrosine phosphorylation of CAS. However, expression of this protein had no effect on morphological transformation, src-mediated actin rearrangements, or anchorage-independent growth of these cells when grown at the src-permissive temperature. Thus, the ability of activated src to mediate cellular transformation is either largely independent of endogenous CAS phosphorylation and/or its association with CAS or, alternatively, the carboxy-terminus of CAS may substitute for endogenous CAS in the process of src-mediated transformation.
多条证据表明，衔接分子p130CAS（Crk相关底物（CAS））是src介导的细胞转化所必需的。CAS已被证明在src转化的细胞中高度酪氨酸磷酸化，并且缺乏CAS结合的src基因变体也无法介导细胞转化。在本报告中，我们研究了CAS磷酸化和/或其与src的结合是否是转化过程的必需要素。在表达v-src温度敏感等位基因的大鼠1成纤维细胞中，CAS羧基末端src结合结构域的表达抑制了src-CAS复合物的形成，也抑制了CAS的酪氨酸磷酸化。然而，当这些细胞在src允许温度下生长时，该蛋白的表达对形态转化、src介导的肌动蛋白重排或这些细胞的非贴壁依赖性生长没有影响。因此，活化的src介导细胞转化的能力要么在很大程度上独立于内源性CAS磷酸化和/或其与CAS的结合，要么在src介导的转化过程中，CAS的羧基末端可以替代内源性CAS。
