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https://hdl.handle.net/2440/68685
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Type: | Journal article |
Title: | An integrin phosphorylation switch the effect of β3 integrin tail phosphorylation on dok1 and talin binding |
Other Titles: | An integrin phosphorylation switch the effect of beta3 integrin tail phosphorylation on dok1 and talin binding |
Author: | Oxley, C. Anthis, N. Lowe, E. Vakonakis, I. Campbell, I. Wegener, K. |
Citation: | Journal of Biological Chemistry, 2008; 283(9):5420-5426 |
Publisher: | Amer Soc Biochemistry Molecular Biology Inc |
Issue Date: | 2008 |
ISSN: | 0021-9258 1083-351X |
Statement of Responsibility: | Camilla L. Oxley, Nicholas J. Anthis, Edward D. Lowe, Ioannis Vakonakis, Iain D. Campbell, and Kate L. Wegener |
Abstract: | Integrins play a fundamental role in cell migration and adhesion; knowledge of how they are regulated and controlled is vital for understanding these processes. Recent work showed that Dok1 negatively regulates integrin activation, presumably by competition with talin. To understand how this occurs, we used NMR spectroscopy and x-ray crystallography to investigate the molecular details of interactions with integrins. The binding affinities of β3 integrin tails for the Dok1 and talin phosphotyrosine binding domains were quantified using 15N-1H hetero-nuclear single quantum correlation titrations, revealing that the unphosphorylated integrin tail binds more strongly to talin than Dok1. Chemical shift mapping showed that unlike talin, Dok1 exclusively interacts with the canonical NPXY motif of the β3 integrin tail. Upon phosphorylation of Tyr747 in the β3 integrin tail, however, Dok1 then binds much more strongly than talin. Thus, we show that phosphorylation of Tyr747 provides a switch for integrin ligand binding. This switch may represent an in vivo mechanism for control of integrin receptor activation. These results have implications for the control of integrin signaling by proteins containing phosphotyrosine binding domains. |
Keywords: | Animals Mice RNA-Binding Proteins Talin DNA-Binding Proteins Integrin beta3 Phosphoproteins Crystallography, X-Ray Nuclear Magnetic Resonance, Biomolecular Cell Adhesion Cell Movement Protein Structure, Tertiary Phosphorylation |
Description: | Received for publication, November 16, 2007, and in revised form, December 20, 2007 Published, JBC Papers in Press, December 21, 2007 |
Rights: | © 2008 by The American Society for Biochemistry and Molecular Biology, Inc. |
DOI: | 10.1074/jbc.M709435200 |
Published version: | http://dx.doi.org/10.1074/jbc.m709435200 |
Appears in Collections: | Aurora harvest 5 Chemistry and Physics publications |
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