ABL-INTERACTOR-1, A NOVEL SH3 PROTEIN-BINDING TO THE CARBOXY-TERMINAL PORTION OF THE ABL PROTEIN, SUPPRESSES V-ABL TRANSFORMING ACTIVITY

A novel cellular protein, Ab1-interactor-1 (Abi-1), which specifically interacts with the carboxy-terminal region of Abl oncoproteins, has been identified in a mouse leukemia cell line. The protein exhibits sequence similarity to homeotic genes, contains several polyproline stretches, and includes a src homology 3 (SH3) domain at its very carboxyl terminus that is required for binding to Abl proteins. The abi-l gene has been mapped to mouse chromosome 2 and is genetically closely linked to the c-abl locus. The gene is widely expressed in the mouse, with highest levels of mRNA found in the bone marrow, spleen, brain, and testes. The Abi-l protein coimmunoprecipitates with v-Abl and serves as a substrate for kinase activity. When overexpressed in NLH-3T3 cells, abi-1 potently suppresses the transforming activity of Abelson leukemia virus expressing the full-length p160(v-ab1) kinase but does not affect the transforming activity of viruses expressing a truncated p90(v-ab1) or v-src kinases. We suggest that the Abi-l protein may serve as a regulator of Abl function in transformation or in signal transduction.