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

J. Biol. Chem., Vol. 279, Issue 28, 28889-28895, July 9, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/28/28889    most recent M402161200v1 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 Calderwood, D. A. Articles by Ginsberg, M. H. Search for Related Content PubMed PubMed Citation Articles by Calderwood, D. A. Articles by Ginsberg, M. H. Social Bookmarking                      What's this?

Competition for Talin Results in Trans-dominant Inhibition of Integrin Activation^*

David A. Calderwood¶, Vera Tai, Gilbert Di Paolo||, Pietro De Camilli||, and Mark H. Ginsberg**

From the Deptartment of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, the Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, and the ^||Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510

The ability of integrin adhesion receptors to undergo rapid changes in affinity for their extracellular ligands (integrin activation) is essential for the development and function of multicellular animals and is dependent on interactions between the integrin subunit-cytoplasmic tail and the cytoskeletal protein talin. Cross-talk among different integrins and between integrins and other receptors impacts many cellular processes including adhesion, spreading, migration, clot retraction, proliferation, and differentiation. One form of integrin cross-talk, transdominant inhibition of integrin activation, occurs when ligand binding to one integrin inhibits the activation of a second integrin. This may be relevant clinically in a number of settings such as during platelet adhesion, leukocyte trans-migration, and angiogenesis. Here we report that competition for talin underlies the trans-dominant inhibition of integrin activation. This conclusion is based on our observations that (i) tails selectively defective in talin binding are unable to mediate trans-dominant inhibition, (ii) trans-dominant inhibition can be reversed by overexpression of integrin binding and activating fragments of talin, and (iii) expression of another non-integrin talin-binding protein, phosphatidylinositol phosphate kinase type I-90, also inhibits integrin activation. Thus, the sequestration of talin by the suppressive species is both necessary and sufficient for trans-dominant inhibition of integrin activation.

Received for publication, February 26, 2004 , and in revised form, May 10, 2004.

^* This work was supported by Grants GM68600, HL31950, AR27214, NS36251, and CA46128 from the National Institutes of Health and a Scientist Development Award from the American Heart Association (to D. A. C.). This is publication number 16429-CB from The Scripps Research Institute. 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.

^** Present address: Dept. of Medicine, University of California, San Diego, La Jolla, CA 92037.

^¶ To whom correspondence should be addressed. E-mail: david.calderwood{at}yale.edu.

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

This article has been cited by other articles:

				C. Kim, T.-L. Lau, T. S. Ulmer, and M. H. Ginsberg Interactions of platelet integrin {alpha}IIb and {beta}3 transmembrane domains in mammalian cell membranes and their role in integrin activation Blood, May 7, 2009; 113(19): 4747 - 4753. [Abstract] [Full Text] [PDF]

				S. Barbero, A. Mielgo, V. Torres, T. Teitz, D. J. Shields, D. Mikolon, M. Bogyo, D. Barila, J. M. Lahti, D. Schlaepfer, et al. Caspase-8 Association with the Focal Adhesion Complex Promotes Tumor Cell Migration and Metastasis Cancer Res., May 1, 2009; 69(9): 3755 - 3763. [Abstract] [Full Text] [PDF]

				D. S. Harburger, M. Bouaouina, and D. A. Calderwood Kindlin-1 and -2 Directly Bind the C-terminal Region of {beta} Integrin Cytoplasmic Tails and Exert Integrin-specific Activation Effects J. Biol. Chem., April 24, 2009; 284(17): 11485 - 11497. [Abstract] [Full Text] [PDF]

				A. del Rio, R. Perez-Jimenez, R. Liu, P. Roca-Cusachs, J. M. Fernandez, and M. P. Sheetz Stretching Single Talin Rod Molecules Activates Vinculin Binding Science, January 30, 2009; 323(5914): 638 - 641. [Abstract] [Full Text] [PDF]

				A. M. Gonzalez, J. Claiborne, and J. C. R. Jones Integrin Cross-talk in Endothelial Cells Is Regulated by Protein Kinase A and Protein Phosphatase 1 J. Biol. Chem., November 14, 2008; 283(46): 31849 - 31860. [Abstract] [Full Text] [PDF]

				M. Bouaouina, Y. Lad, and D. A. Calderwood The N-terminal Domains of Talin Cooperate with the Phosphotyrosine Binding-like Domain to Activate {beta}1 and {beta}3 Integrins J. Biol. Chem., March 7, 2008; 283(10): 6118 - 6125. [Abstract] [Full Text] [PDF]

				D. Bouvard, A. Aszodi, G. Kostka, M. R. Block, C. Albiges-Rizo, and R. Fassler Defective osteoblast function in ICAP-1-deficient mice Development, July 15, 2007; 134(14): 2615 - 2625. [Abstract] [Full Text] [PDF]

				Y. Sun, K. Ling, M. P. Wagoner, and R. A. Anderson Type I{gamma} phosphatidylinositol phosphate kinase is required for EGF-stimulated directional cell migration J. Cell Biol., July 10, 2007; 178(2): 297 - 308. [Abstract] [Full Text] [PDF]

				C. M. Meighan and J. E. Schwarzbauer Control of C. elegans hermaphrodite gonad size and shape by vab-3/Pax6-mediated regulation of integrin receptors Genes & Dev., July 1, 2007; 21(13): 1615 - 1620. [Abstract] [Full Text] [PDF]

				P. Dominguez-Gimenez, N. H. Brown, and M. D. Martin-Bermudo Integrin-ECM interactions regulate the changes in cell shape driving the morphogenesis of the Drosophila wing epithelium J. Cell Sci., March 15, 2007; 120(6): 1061 - 1071. [Abstract] [Full Text] [PDF]

				A. Kasirer-Friede, B. Moran, J. Nagrampa-Orje, K. Swanson, Z. M. Ruggeri, B. Schraven, B. G. Neel, G. Koretzky, and S. J. Shattil ADAP is required for normal {alpha}IIb{beta}3 activation by VWF/GP Ib-IX-V and other agonists Blood, February 1, 2007; 109(3): 1018 - 1025. [Abstract] [Full Text] [PDF]

				Y. Benninger, H. Colognato, T. Thurnherr, R. J. M. Franklin, D. P. Leone, S. Atanasoski, K.-A. Nave, C. ffrench-Constant, U. Suter, and J. B. Relvas Beta1-integrin signaling mediates premyelinating oligodendrocyte survival but is not required for CNS myelination and remyelination. J. Neurosci., July 19, 2006; 26(29): 7665 - 7673. [Abstract] [Full Text] [PDF]

				G. Tanentzapf, M. D. Martin-Bermudo, M. S. Hicks, and N. H. Brown Multiple factors contribute to integrin-talin interactions in vivo J. Cell Sci., April 15, 2006; 119(8): 1632 - 1644. [Abstract] [Full Text] [PDF]

				A. R. Gingras, W. H. Ziegler, R. Frank, I. L. Barsukov, G. C. K. Roberts, D. R. Critchley, and J. Emsley Mapping and Consensus Sequence Identification for Multiple Vinculin Binding Sites within the Talin Rod J. Biol. Chem., November 4, 2005; 280(44): 37217 - 37224. [Abstract] [Full Text] [PDF]

				B. Ratnikov, C. Ptak, J. Han, J. Shabanowitz, D. F. Hunt, and M. H. Ginsberg Talin phosphorylation sites mapped by mass spectrometry J. Cell Sci., November 1, 2005; 118(21): 4921 - 4923. [Full Text] [PDF]

				D. J. Powner, R. M. Payne, T. R. Pettitt, M. L. Giudici, R. F. Irvine, and M. J. O. Wakelam Phospholipase D2 stimulates integrin-mediated adhesion via phosphatidylinositol 4-phosphate 5-kinase I{gamma}b J. Cell Sci., July 1, 2005; 118(13): 2975 - 2986. [Abstract] [Full Text] [PDF]

				D. M. Cohen, H. Chen, R. P. Johnson, B. Choudhury, and S. W. Craig Two Distinct Head-Tail Interfaces Cooperate to Suppress Activation of Vinculin by Talin J. Biol. Chem., April 29, 2005; 280(17): 17109 - 17117. [Abstract] [Full Text] [PDF]

				S. Y. Lee, S. Voronov, K. Letinic, A. C. Nairn, G. Di Paolo, and P. De Camilli Regulation of the interaction between PIPKI{gamma} and talin by proline-directed protein kinases J. Cell Biol., February 28, 2005; 168(5): 789 - 799. [Abstract] [Full Text] [PDF]

				J. R. Morgan, G. Di Paolo, H. Werner, V. A. Shchedrina, M. Pypaert, V. A. Pieribone, and P. De Camilli A role for talin in presynaptic function J. Cell Biol., October 11, 2004; 167(1): 43 - 50. [Abstract] [Full Text] [PDF]