SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins

Expression of the src homology 3 (SH3)-encoding, expressed in tumorigenic a strocytes (SETA) gene is associated with astrocyte transformation in cultur e and tumors in the adult brain. SETA binds to the apoptosis regulator apop tosis-linked gene 2 (ALG-2) interacting protein 1 (AIP I), and modulates ap optosis in astrocytes. The predicted protein structure of SETA revealed two SH3 domains, while related proteins were reported to have three. Here we r eport the identification of an additional SH3 domain N-terminal to the prev iously identified SETA sequence. Yeast two-hybrid screening of a p53(-/-) a strocyte cDNA library with this; SH3 domain identified a novel gene, SETA b inding protein I (SB1), with 55% amino acid identity to the renal tumor ant igen, NY-REN-45. In vitro confrontation and coimmunoprecipitation experimen ts confirmed the binding of SB1 to SETA. Evidence that SETA binds to the CD 2 protein, the proto-oncogene c-Cbl, and the signal transduction molecule G rb2, and can dimerize via its C-terminal coiled coil (CC) domain is also pr esented. (C) 2000 Elsevier Science Inc. All rights reserved.