Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian enabled (Mena) by c-Abl kinase.

Mammalian Enabled (Mena) is a mammalian homologue of Drosophila Enabled (Ena), which genetically interacts with Drosophila Abl tyrosine kinase. The signaling pathway involving c-Abl and Mena (Ena) is not fully understood. To find molecules that participate in the c-Abl/Mena pathway, we searched for Mena-binding proteins using a yeast two-hybrid system. ...
We identified Abl interactor 1 (Abi-1), which is known to interact with c-Abl, as a binding protein for Mena. Binding analysis revealed that the Ena/Vasp homology 1 domain of Mena and the polyproline structure of Abi-1 are necessary for the interaction. The interaction between Mena and Abi-1 was also observed in a mammalian expression system. Importantly, Abi-1 dramatically promoted c-Abl-mediated tyrosine phosphorylation of Mena but not other substrates such as c-Cbl. Mutational analysis demonstrated that the phosphorylation site of Mena is Tyr-296. Our results suggest that Abi-1 regulates c-Abl-mediated phosphorylation of Mena by interacting with both proteins.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Alternative Splicing, Amino Acid Sequence, Animals, Binding Sites, Carrier Proteins, Cell Line, Cytoskeletal Proteins, DNA Mutational Analysis, DNA, Complementary, DNA-Binding Proteins, Gene Library, Glutathione Transferase, Homeodomain Proteins, Humans, Mice, Microscopy, Fluorescence, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins c-abl, Rats, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Signal Transduction, Two-Hybrid System Techniques, Tyrosine
J. Biol. Chem.
Date: Jun. 13, 2003
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