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

Borinstein SC, Hyatt MA, Sykes VW, Straub RE, Lipkowitz S, Boulter J, Bogler O
Cell Signal. 2000 12 (11-12): 769-79

PMID: 11152963

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.

MeSH Terms (31)

Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Antigens, Neoplasm Astrocytes Carrier Proteins CD2 Antigens Cells, Cultured Dimerization Exons Gene Deletion Gene Library GRB2 Adaptor Protein Mice Molecular Sequence Data Neoplasm Proteins Nerve Tissue Proteins Precipitin Tests Protein Binding Protein Isoforms Proteins Protein Structure, Tertiary Proto-Oncogene Proteins Proto-Oncogene Proteins c-cbl Rats Sequence Alignment src Homology Domains Tumor Cells, Cultured Tumor Suppressor Protein p53 Two-Hybrid System Techniques Ubiquitin-Protein Ligases

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