Inhibition of c-Abl Tyrosine Kinase Activity by Filamentous Actin
| Autor: | Jean Y. J. Wang, Pamela J. Woodring, Tony Hunter |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
biology
MAP kinase kinase kinase Cyclin-dependent kinase 4 Cyclin-dependent kinase 2 macromolecular substances Cell Biology Mitogen-activated protein kinase kinase Biochemistry Molecular biology MAP2K7 hemic and lymphatic diseases biology.protein ASK1 Cyclin-dependent kinase 9 Kinase activity neoplasms Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 276:27104-27110 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m100559200 |
| Popis: | The catalytic activity of c-Abl tyrosine kinase is reduced in fibroblasts that are detached from the extracellular matrix. We report here that a deletion of the extreme C terminus of c-Abl (ΔF-actin c-Abl) can partially restore kinase activity to c-Abl from detached cells. Because the extreme C terminus of c-Abl contains a consensus F-actin binding motif, we investigated the effect of F-actin on c-Abl tyrosine kinase activity. We found that F-actin can inhibit the kinase activity of purified c-Abl protein. Mutations of the extreme C-terminal region of c-Abl disrupted both the binding of c-Abl to F-actin and the inhibition of c-Abl by F-actin. Mutations of the SH3, SH2, and DNA binding domains did not abolish the inhibition of c-Abl kinase by F-actin. Catalytic domain substitutions that affect the regulation of c-Abl by the retinoblastoma protein or the ataxia telangiectasia-mutated kinase also did not abolish the inhibition of c-Abl by F-actin. Interestingly, among these c-Abl mutants, only the ΔF-actin c-Abl retained kinase activity in detached cells. Taken together, the data suggest that F-actin is an inhibitor of the c-Abl tyrosine kinase and that this inhibition contributes in part to the reduced Abl kinase activity in detached cells. |
| Databáze: | OpenAIRE |
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