C-terminal Src kinase associates with ligand-stimulated insulin-like growth factor-I receptor
C-terminal Src kinase associates with ligand-stimulated insulin-like growth factor-I receptor
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DOI：
10.1074/jbc.274.9.5422
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发表时间：
1999-02-26
影响因子：
4.8
通讯作者：
Eckhart, W
中科院分区：
文献类型：
--
作者：
Arbet-Engels, C;Tartare-Deckert, S;Eckhart, W
胰岛素样生长因子-I受体（IGF-IR）蛋白酪氨酸激酶的表达增加发生在几种癌症中，并诱导成纤维细胞系的肿瘤转化。转化的表型可以通过干扰IGF-IR的功能来逆转。IGF-IR是许多病毒和细胞癌蛋白转化所必需的，包括SV 40大T抗原、Ras、Raf和Src。IGF-IR在体外是Src的底物，在v-Src转化细胞中被磷酸化。Ne观察到IGF-IR和IR与C-末端Src激酶（CSK）相关。我们发现CSK的SH 2结构域与IGF-IR和IR的酪氨酸磷酸化形式结合。我们确定了IGF-IR和IR中负责这种相互作用的酪氨酸残基。我们还观察到，用IGF-I或胰岛素刺激的成纤维细胞显示出c-Src酪氨酸激酶活性的快速和短暂的降低。结果表明，c-Src和CSK参与IGF-IR和IR信号转导，CSK与IGF-IR的相互作用可能在IGF-I刺激后c-Src活性降低中起作用。
Increased expression of the insulin-like growth factor-I receptor (IGF-IR) protein-tyrosine kinase occurs in several kinds of cancer and induces neoplastic transformation in fibroblast cell lines. The transformed phenotype can be reversed by interfering with the function of the IGF-IR. The IGF-IR is required for transformation by a number of viral and cellular oncoproteins, including SV40 large T antigen, Ras, Raf, and Src. The IGF-IR is a substrate for Src in vitro and is phosphorylated in v-Src-transformed cells. Ne observed that the IGF-IR and IR associated with the C-terminal Src kinase (CSK) following ligand stimulation. We found that the SH2 domain of CSK binds to the tyrosine-phosphorylated form of IGF-IR and IR We determined the tyrosine residues in the IGF-IR and in the IR responsible for this interaction. We also observed that fibroblasts stimulated with IGF-I or insulin showed a rapid and transient decrease in c-Src tyrosine kinase activity. The results suggest that c-Src and CSK are involved in IGF-IR and IR signaling and that the interaction of CSK with the IGF-IR may play a role in the decrease in c-Src activity following IGF-I stimulation.