Abi enhances Abl-mediated CDC2 phosphorylation and inactivation.
Abelson tyrosine kinase (Abl) is a non-receptor tyrosine kinase which is frequently coupled with adaptor proteins to interact with its substrates for the regulation of cytoskeleton rearrangement, cell growth and apoptosis in response to a variety of biological stimuli. The Abl interactor (Abi) family members were first identified as adaptor proteins of Abl for regulating Abl transforming and kinase activity. In the present study, we used a yeast two-hybrid screen to identify Cdc2 as a novel Abi-binding protein. This finding led us to investigate the role of Abi in linking Abl and Cdc2. These three proteins formed a trimeric complex in Drosophila and mammalian cells. The expression of Abi in cells greatly enhanced the formation of the Abl-Cdc2 complex, suggesting that Abi functions as an adaptor protein facilitating the binding between Abl and Cdc2. We show that Abi promotes Abl-mediated phosphorylation of Cdc2 at tyrosine 15 and inactivation of Cdc2 kinase activity. Furthermore, coexpression of Abl and Abi in Drosophila S2 cells led to suppression of cell growth. These data suggest that Abl signaling may be involved in the downregulation of Cdc2 kinase in cell cycle control.
Lin
Tzu-Yang
TY
Division of Molecular and Genomic Medicine, National Health Research Institutes, Taipei, Taiwan.
Huang
Chiu-Hui
CH
Chou
Wen-Gang
WG
Juang
Jyh-Lyh
JL
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019556:COS Cells; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019143:Evolution, Molecular; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D008957:Models, Genetic; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques
C513733:ABI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D005982:Glutathione Transferase; D016315:Proto-Oncogene Proteins c-abl; D016203:CDC2 Protein Kinase