title: Drosophila abelson interacting protein (dAbi) is a positive regulator of abelson tyrosine kinase activity.
abstract: Human and mouse Abelson interacting proteins (Abi) are SH3-domain containing proteins that bind to the proline-rich motifs of the Abelson protein tyrosine kinase. We report a new member of this gene family, a Drosophila Abi (dAbi) that is a substrate for Abl kinase and that co-immunoprecipitates with Abl if the Abi SH3 domain is intact. We have identified a new function for both dAbi and human Abi-2 (hAbi-2). Both proteins activate the kinase activity of Abl as assayed by phosphorylation of the Drosophila Enabled (Ena) protein. Removal of the dAbi SH3 domain eliminates dAbi's activation of Abl kinase activity. dAbi is an unstable protein in cells and is present at low steady state levels but its protein level is increased coincident with phosphorylation by Abl kinase. Expression of the antisense strand of dAbi reduces dAbi protein levels and abolishes activation of Abl kinase activity. Modulation of Abi protein levels may be an important mechanism for regulating the level of Abl kinase activity in the cell.
authors.affiliation: National Health Research Institute, 128 Yen-Chiu-Yuan Road, Sec. 2, Taipei, Taiwan.
authors.forename: J L
authors.initials: JL
authors.lastname: Juang
authors.forename: F M
authors.initials: FM
authors.lastname: Hoffmann
mesh_terms: D000011:Abelson murine leukemia virus / Q000201:enzymology; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D003001:Cloning, Molecular; D016384:Consensus Sequence; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D004789:Enzyme Activation; D019143:Evolution, Molecular; D018398:Homeodomain Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D016374:Oncogene Proteins v-abl / Q000737:chemistry / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000502:physiology*; D016315:Proto-Oncogene Proteins c-abl / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014162:Transfection; D018909:src Homology Domains
chemical_list: C513733:ABI1 protein, human; C096831:ABI2 protein, human; C121808:Abi protein, Drosophila; C513734:Abi1 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D016374:Oncogene Proteins v-abl; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl