Identification and characterization of a novel Rho GTPase activating protein implicated in receptor-mediated endocytosis

Abstract

Cbl-interacting protein of 85 kDa (CIN85) is a recently identified adaptor protein involved in the endocytic process of several receptor tyrosine kinases. Here we have identified a novel RhoGAP, CIN85 associated multi-domain containing RhoGAP1 (CAMGAP1) as a binding protein for CIN85. CAMGAP1 is composed of an Src homology 3 (SH3) domain, multiple WW domains, a proline-rich region, a PH domain and a RhoGAP domain, and has the domain architecture similar to ARHGAP9 and ARHGAP12. CAMGAP1 mRNA is widely distributed in murine tissues. Biochemical assays showed its GAP activity toward Rac1 and Cdc42. Protein binding and expression studies indicated that the second SH3 domain of CIN85 binds to a proline-rich region of CAMGAP1. Overexpression of a truncated form of CAMGAP1 interferes with the internalization of transferrin receptors, suggesting that CAM-GAP1 may play a role in clathrin-mediated endocytosis.

Overexpression of CIN85 suppresses the growth of herpes simplex virus in HeLa cells

“…We identified this protein independently as SH3 domain kinase binding-protein 1 (SH3KBP1) and reported that its gene maps to the human X chromosome region p22.1 -p21.3 [2]. CIN85 and its rat homolog, Ruk/SETA [3,4], are widely expressed in a variety of tissues and form complexes with many signaling proteins via its PRR [3][4][5][6][7] or SH3 domains [8][9][10][11]. These complexes play a role in various biological functions, including control of receptor tyrosine kinase (RTK) signaling [6,7,10 -12], rearrangement of the actin cytoskeleton [13], and apoptosis in neuronal cells [3,14].…”