The Cdc42 target ACK2 interacts with sorting nexin 9 (SH3PX1) to regulate epidermal growth factor receptor degradation.

摘要: Activated Cdc42-associated kinase-2 (ACK2) is a non-receptor tyrosine kinase that serves as specific effector for Cdc42, Rho family small G-protein. Recently, we have found ACK2 directly interacts with clathrin heavy chain through clathrin-binding motif conserved in all endocytic adaptor proteins and regulates assembly, suggesting plays role clathrin-coated vesicle endocytosis (Yang, W., Lo, C. G., Dispenza, T., Cerione, R. A. (2001)J. Biol. Chem. 276, 17468–17473). Here report the identification of another binding partner has previously been implicated endocytosis, namely sorting nexin protein SH3PX1 (sorting 9). The interaction occurs between proline-rich domain Src homology 3 (SH3) SH3PX1. Co-immunoprecipitation studies indicate ACK2, clathrin, form complex cells. Epidermal growth factor (EGF) stimulated phosphorylation SH3PX1, whereas co-transfection resulted constitutive However, kinase-dead mutant ACK2(K158R) blocked EGF-induced indicating EGF-stimulated mediated by ACK2. EGF receptor levels were significantly decreased following stimulation cells co-expressing thus highlighting novel working together to promote degradation receptor.