title: SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins.
abstract: Expression of the src homology 3 (SH3)-encoding, expressed in tumorigenic astrocytes (SETA) gene is associated with astrocyte transformation in culture and tumors in the adult brain. SETA binds to the apoptosis regulator apoptosis-linked gene 2 (ALG-2) interacting protein 1 (AIP1), and modulates apoptosis in astrocytes. The predicted protein structure of SETA revealed two SH3 domains, while related proteins were reported to have three. Here we report the identification of an additional SH3 domain N-terminal to the previously identified SETA sequence. Yeast two-hybrid screening of a p53(-/-) astrocyte cDNA library with this SH3 domain identified a novel gene, SETA binding protein 1 (SB1), with 55% amino acid identity to the renal tumor antigen, NY-REN-45. In vitro confrontation and co-immunoprecipitation experiments confirmed the binding of SB1 to SETA. Evidence that SETA binds to the CD2 protein, the proto-oncogene c-Cbl, and the signal transduction molecule Grb2, and can dimerize via its C-terminal coiled coil (CC) domain is also presented.
authors.affiliation: Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Borinstein
authors.forename: M A
authors.initials: MA
authors.lastname: Hyatt
authors.forename: V W
authors.initials: VW
authors.lastname: Sykes
authors.forename: R E
authors.initials: RE
authors.lastname: Straub
authors.forename: S
authors.initials: S
authors.lastname: Lipkowitz
authors.forename: J
authors.initials: J
authors.lastname: Boulter
authors.forename: O
authors.initials: O
authors.lastname: Bogler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry; D001253:Astrocytes / Q000378:metabolism; D018801:CD2 Antigens / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D019281:Dimerization; D005091:Exons / Q000235:genetics; D051380:GRB2 Adaptor Protein; D017353:Gene Deletion; D015723:Gene Library; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D051381:Rats; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D018801:CD2 Antigens; D002352:Carrier Proteins; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; C495950:Grb2 protein, rat; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011506:Proteins; D011518:Proto-Oncogene Proteins; C498782:Sh3kbp1 protein, mouse; C411889:Sh3kbp1 protein, rat; C419486:Shkbp1 protein, mouse; D016159:Tumor Suppressor Protein p53; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C493849:Cbl protein, mouse