Take H, Watanabe S, Takeda K, Yu Z X, Iwata N, Kajigaya S
Hematology Branch, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Biochem Biophys Res Commun. 2000 Feb 16;268(2):321-8. doi: 10.1006/bbrc.2000.2147.
The c-Cbl protooncogene product is a prominent substrate of protein tyrosine kinases and is rapidly tyrosine-phosphorylated upon stimulation of a wide variety of cell-surface receptors. We have identified a novel c-Cbl-interacting protein termed CIN85 with a molecular mass of 85 kDa which shows similarity to adaptor proteins, CMS and CD2AP. CIN85 mRNA is expressed ubiquitously in normal human tissues and cancer cell lines analyzed. CIN85 was basally associated with c-Cbl. For interaction of CIN85 with c-Cbl, the second SH3 domain of CIN85 was shown to serve as a central player. The CIN85-c-Cbl association was enhanced shortly after stimulation of 293 cells with epidermal growth factor (EGF) and gradually diminished to a basal level, which correlated with a tyrosine phosphorylation level of c-Cbl. Our results suggest that CIN85 may play a specific role in the EGF receptor-mediated signaling cascade via its interaction with c-Cbl.
原癌基因c-Cbl的产物是蛋白酪氨酸激酶的主要底物，在多种细胞表面受体受到刺激后会迅速发生酪氨酸磷酸化。我们鉴定出一种新的与c-Cbl相互作用的蛋白，称为CIN85，分子量为85 kDa，与衔接蛋白CMS和CD2AP具有相似性。在所分析的正常人体组织和癌细胞系中，CIN85 mRNA普遍表达。CIN85与c-Cbl呈基础关联。对于CIN85与c-Cbl的相互作用，CIN85的第二个SH3结构域被证明起核心作用。在用表皮生长因子（EGF）刺激293细胞后不久，CIN85与c-Cbl的结合增强，随后逐渐降至基础水平，这与c-Cbl的酪氨酸磷酸化水平相关。我们的结果表明，CIN85可能通过与c-Cbl相互作用在EGF受体介导的信号级联反应中发挥特定作用。
