Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity.
A protein has been identified that interacts specifically with both the Src homologous 3 (SH3) domain and carboxy-terminal sequences of the c-Abl tyrosine kinase. The cDNA encoding the Abl interactor protein (Abi-2), was isolated from a human lymphocyte library using the yeast two-hybrid system with the Abl SH3 domain as bait. Abi-2 binds to c-Abl in vitro and in vivo. Abi-2 is a novel protein that contains an SH3 domain and proline-rich sequences critical for binding to c-Abl. A basic region in the amino terminus of Abi-2 is homologous to the DNA-binding sequence of homeo-domain proteins. We show that Abi-2 is a substrate for the c-Abl tyrosine kinase. Expression of an Abi-2 mutant protein that lacks sequences required for binding to the Abl SH3 domain but retains binding to the Abl carboxyl terminus activates the transforming capacity of c-Abl. The properties of Abi-2 are consistent with a dual role as regulator and potential effector of the c-Abl protein and suggest that Abi-2 may function as a tumor suppressor in mammalian cells.
Dai
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Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.
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D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001665:Binding Sites; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D011392:Proline; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000276:immunology / Q000378:metabolism*; D012313:RNA; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014018:Tissue Distribution; D018909:src Homology Domains
C096831:ABI2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D012313:RNA; D011392:Proline; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl