Protein-tyrosine kinases regulate the phosphorylation, protein interactions, subcellular distribution, and activity of p21ras GTPase-activating protein
Protein-tyrosine kinases regulate the phosphorylation, protein interactions, subcellular distribution, and activity of p21ras GTPase-activating protein
复制标题
蛋白酪氨酸激酶调节 p21ras GTP 酶激活蛋白的磷酸化、蛋白相互作用、亚细胞分布和活性
DOI：
10.1128/mcb.11.4.1804-1812.1991
复制
发表时间：
1991
影响因子：
5.3
通讯作者：
'. Christineellis
中科院分区：
文献类型：
--
作者：
M. Moran;P. Polakis;F. McCormick;T. Pawson;'. Christineellis
p21 ras GTP酶激活蛋白（GAP）通过刺激其内在的GTP酶活性下调p21 ras。GAP主要作为单体存在于正常细胞的胞质溶胶中。然而，在表达活化的细胞质蛋白酪氨酸激酶p60 v-src或用表皮生长因子刺激的细胞中，GAP在酪氨酸和丝氨酸上磷酸化，并与62和190 kDa的两种磷蛋白（p62和p190）形成不同的复合物。在v-src转化的Rat-2细胞中，一小部分GAP与高度酪氨酸磷酸化的p62结合形成位于质膜和胞质溶胶中的复合物。与此相反，大多数GAP进入一个独特的复合物与p190是专门的胞质，主要含有磷酸丝氨酸。表皮生长因子刺激也诱导大鼠成纤维细胞中单体GAP向更高分子量物质的显著转化。GAP-p190复合物依赖于磷酸化并显示出降低的GAP活性。这些结果表明，蛋白酪氨酸激酶诱导GAP形成多个异聚体复合物，这是强有力的候选人的调节剂或靶点的p21 ras。
The p21ras GTPase-activating protein (GAP) down-regulates p21ras by stimulating its intrinsic GTPase activity. GAP is found predominantly as a monomer in the cytosol of normal cells. However, in cells expressing an activated cytoplasmic protein-tyrosine kinase, p60v-src, or stimulated with epidermal growth factor, GAP becomes phosphorylated on tyrosine and serine and forms distinct complexes with two phosphoproteins of 62 and 190 kDa (p62 and p190). In v-src-transformed Rat-2 cells, a minor fraction of GAP associates with the highly tyrosine phosphorylated p62 to form a complex that is localized at the plasma membrane and in the cytosol. In contrast, the majority of GAP enters a distinct complex with p190 that is exclusively cytosolic and contains predominantly phosphoserine. Epidermal growth factor stimulation also induces a marked conversion of monomeric GAP to higher-molecular-weight species in rat fibroblasts. The GAP-p190 complex is dependent on phosphorylation and shows reduced GAP activity. These results indicate that protein-tyrosine kinases induce GAP to form multiple heteromeric complexes, which are strong candidates for regulators or targets of p21ras.
将蛋白质转移到膜上有利于溴化氰裂解和二维蛋白水解图谱。
影响因子：
8
作者：
Luo,K;Hurley,TR;Sefton,BM
通讯作者：
Sefton,BM
通过 cDNA 文库的磷酸酪氨酸抗体筛选鉴定出新型酪氨酸激酶。
影响因子：
5.3
作者：
Kornbluth,S;Paulson,KE;Hanafusa,H
通讯作者：
Hanafusa,H