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, Abl-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-1 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-1 protein coimmunoprecipitates with v-Abl and serves as a substrate for kinase activity. When overexpressed in NIH-3T3 cells, abi-1 potently suppresses the transforming activity of Abelson leukemia virus expressing the full-length p160v-abl kinase but does not affect the transforming activity of viruses expressing a truncated p90v-abl or v-src kinases. We suggest that the Abi-1 protein may serve as a regulator of Abl function in transformation or in signal transduction.
Shi
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Howard Hughes Medical Institute, Columbia University, College of Physicians and Surgeons, New York 10032, USA.
Alin
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Goff
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D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002471:Cell Transformation, Neoplastic; D002874:Chromosome Mapping; D002999:Clone Cells; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016374:Oncogene Proteins v-abl / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D012333:RNA, Messenger; D011817:Rabbits; D014018:Tissue Distribution; D018909:src Homology Domains
C513734:Abi1 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D016374:Oncogene Proteins v-abl; D012333:RNA, Messenger