HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 9, 5420-5426, February 29, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/9/5420    most recent M709435200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oxley, C. L. Articles by Wegener, L. Search for Related Content PubMed PubMed Citation Articles by Oxley, C. L. Articles by Wegener, L. Related Collections Papers Of The Week Social Bookmarking                      What's this?

An Integrin Phosphorylation Switch

THE EFFECT OF β3 INTEGRIN TAIL PHOSPHORYLATION ON DOK1 AND TALIN BINDING^*

From the Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom

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.

Received for publication, November 16, 2007 , and in revised form, December 20, 2007.

^* This work was supported by grants from the Wellcome Trust (to C. L. O., I. D. C., I. V., and E. D. L.); Rhodes Trust (to N. J. A.); National Institutes of Health Cell migration consortium (to K. L. W.), and Marie Curie Fellowships (to I. V.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains a protein structure file.

This article was selected as a Paper of the Week.

The atomic coordinates and structure factors (code 2v76) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

¹ To whom correspondence should be addressed. Tel.: 44-1865-275772; Fax: 44-1865-275253; E-mail: kate.wegener{at}bioch.ox.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. T. Goult, N. Bate, N. J. Anthis, K. L. Wegener, A. R. Gingras, B. Patel, I. L. Barsukov, I. D. Campbell, G. C. K. Roberts, and D. R. Critchley The Structure of an Interdomain Complex That Regulates Talin Activity J. Biol. Chem., May 29, 2009; 284(22): 15097 - 15106. [Abstract] [Full Text] [PDF]

				M. Moser, K. R. Legate, R. Zent, and R. Fassler The Tail of Integrins, Talin, and Kindlins Science, May 15, 2009; 324(5929): 895 - 899. [Abstract] [Full Text] [PDF]

				K. R. Legate, S. A. Wickstrom, and R. Fassler Genetic and cell biological analysis of integrin outside-in signaling Genes & Dev., February 15, 2009; 23(4): 397 - 418. [Abstract] [Full Text] [PDF]

				D. S. Harburger and D. A. Calderwood Integrin signalling at a glance J. Cell Sci., January 15, 2009; 122(2): 159 - 163. [Full Text] [PDF]

				J. A. Askari, P. A. Buckley, A. P. Mould, and M. J. Humphries Linking integrin conformation to function J. Cell Sci., January 15, 2009; 122(2): 165 - 170. [Abstract] [Full Text] [PDF]

				K. R. Legate and R. Fassler Mechanisms that regulate adaptor binding to {beta}-integrin cytoplasmic tails J. Cell Sci., January 15, 2009; 122(2): 187 - 198. [Abstract] [Full Text] [PDF]