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Specific integrin α and β chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms

Specific integrin α and β chain phosphorylations regulate LFA-1 activation through... Integrins are adhesion receptors that are crucial to the functions of multicellular organisms. Integrin-mediated adhesion is a complex process that involves both affinity regulation and cytoskeletal coupling, but the molecular mechanisms behind this process have remained incompletely understood. In this study, we report that the phosphorylation of each cytoplasmic domain of the leukocyte function-associated antigen-1 integrin mediates different modes of integrin activation. α Chain phosphorylation on Ser1140 is needed for conformational changes in the integrin after chemokine- or integrin ligand–induced activation or after activation induced by active Rap1 (Rap1V12). In contrast, the β chain Thr758 phosphorylation mediates selective binding to 14-3-3 proteins in response to inside-out activation through the T cell receptor, resulting in cytoskeletal rearrangements. Thus, site-specific phosphorylation of the integrin cytoplasmic domains is important for the dynamic regulation of these complex receptors in cells. Footnotes S.C. Fagerholm and T.J. Hilden contributed equally to this paper. Abbreviations used in this paper: ICAM, intercellular adhesion molecule; J, Jurkat; LFA-1, leukocyte function-associated antigen-1; sICAM, soluble ICAM; TCR, T cell receptor; wt, wild-type. Submitted: 4 April 2005 Accepted: 17 October 2005 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

Specific integrin α and β chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms

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References (62)

Publisher
Rockefeller University Press
Copyright
© 2005 Rockefeller University Press
ISSN
0021-9525
eISSN
1540-8140
DOI
10.1083/jcb.200504016
pmid
16301335
Publisher site
See Article on Publisher Site

Abstract

Integrins are adhesion receptors that are crucial to the functions of multicellular organisms. Integrin-mediated adhesion is a complex process that involves both affinity regulation and cytoskeletal coupling, but the molecular mechanisms behind this process have remained incompletely understood. In this study, we report that the phosphorylation of each cytoplasmic domain of the leukocyte function-associated antigen-1 integrin mediates different modes of integrin activation. α Chain phosphorylation on Ser1140 is needed for conformational changes in the integrin after chemokine- or integrin ligand–induced activation or after activation induced by active Rap1 (Rap1V12). In contrast, the β chain Thr758 phosphorylation mediates selective binding to 14-3-3 proteins in response to inside-out activation through the T cell receptor, resulting in cytoskeletal rearrangements. Thus, site-specific phosphorylation of the integrin cytoplasmic domains is important for the dynamic regulation of these complex receptors in cells. Footnotes S.C. Fagerholm and T.J. Hilden contributed equally to this paper. Abbreviations used in this paper: ICAM, intercellular adhesion molecule; J, Jurkat; LFA-1, leukocyte function-associated antigen-1; sICAM, soluble ICAM; TCR, T cell receptor; wt, wild-type. Submitted: 4 April 2005 Accepted: 17 October 2005

Journal

The Journal of Cell BiologyRockefeller University Press

Published: Nov 21, 2005

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