Two distinct phosphorylation pathways have additive effects on Abl family kinase activation Journal Article
| Authors: | Tanis, K. Q.; Veach, D.; Duewel, H. S.; Bornmann, W. G.; Koleske, A. J. |
| Article Title: | Two distinct phosphorylation pathways have additive effects on Abl family kinase activation |
| Abstract: | The activities of the related Abl and Arg nonreceptor tyrosine kinases are kept under tight control in cells, but exposure to several different stimuli results in a two- to fivefold stimulation of kinase activity. Following the breakdown of inhibitory intramolecular interactions, Abl activation requires phosphorylation on several tyrosine residues, including a tyrosine in its activation loop. These activating phosphorylations have been proposed to occur either through autophosphorylation by Abl in trans or through phosphorylation of Abl by the Src nonreceptor tyrosine kinase. We show here that these two pathways mediate phosphorylation at distinct sites in Abl and Arg and have additive effects on Abl and Arg kinase activation. Abl and Arg autophosphorylate at several sites outside the activation loop, leading to 5.2- and 6.2-fold increases in kinase activity, respectively. We also find that the Src family kinase Hck phosphorylates the Abl and Arg activation loops, leading to an additional twofold stimulation of kinase activity. The autoactivation pathway may allow Abl family kinases to integrate or amplify cues relayed by Src family kinases from cell surface receptors. |
| Keywords: | signal transduction; controlled study; unclassified drug; human cell; proto-oncogene proteins; protein conformation; animals; mice; embryo; cell line; enzyme activation; enzyme activity; abelson kinase; protein tyrosine kinase; tyrosine; autophosphorylation; phosphorylation; enzyme phosphorylation; recombinant fusion proteins; enzyme inhibitors; molecular structure; protein-tyrosine kinases; molecular interaction; protein family; multigene family; enzyme active site; cell surface receptor; proto-oncogene proteins c-abl; humans; human; priority journal; article; protein arg; proto-oncogene proteins c-hck |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 23 |
| Issue: | 11 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2003-06-01 |
| Start Page: | 3884 |
| End Page: | 3896 |
| Language: | English |
| DOI: | 10.1128/mcb.23.11.3884-3896.2003 |
| PUBMED: | 12748290 |
| PROVIDER: | scopus |
| PMCID: | PMC155218 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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