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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Binding Sites, Cell Transformation, Neoplastic, Cloning, Molecular, Homeodomain Proteins, Humans, Lymphocytes, Molecular Sequence Data, Mutation, Proline, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-abl, RNA, Sequence Homology, Amino Acid, Substrate Specificity, Tissue Distribution, src Homology Domains
Genes Dev.
Date: Nov. 01, 1995
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