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.
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21 November 2005
Article|
November 21 2005
Specific integrin α and β chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms
Susanna C. Fagerholm,
Susanna C. Fagerholm
Division of Biochemistry, Faculty of Biosciences, University of Helsinki, FIN-00014 Helsinki, Finland
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Tiina J. Hilden,
Tiina J. Hilden
Division of Biochemistry, Faculty of Biosciences, University of Helsinki, FIN-00014 Helsinki, Finland
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Susanna M. Nurmi,
Susanna M. Nurmi
Division of Biochemistry, Faculty of Biosciences, University of Helsinki, FIN-00014 Helsinki, Finland
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Carl G. Gahmberg
Carl G. Gahmberg
Division of Biochemistry, Faculty of Biosciences, University of Helsinki, FIN-00014 Helsinki, Finland
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Susanna C. Fagerholm
Division of Biochemistry, Faculty of Biosciences, University of Helsinki, FIN-00014 Helsinki, Finland
Tiina J. Hilden
Division of Biochemistry, Faculty of Biosciences, University of Helsinki, FIN-00014 Helsinki, Finland
Susanna M. Nurmi
Division of Biochemistry, Faculty of Biosciences, University of Helsinki, FIN-00014 Helsinki, Finland
Carl G. Gahmberg
Division of Biochemistry, Faculty of Biosciences, University of Helsinki, FIN-00014 Helsinki, Finland
Correspondence to Carl G. Gahmberg: [email protected]
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.
Received:
April 04 2005
Accepted:
October 17 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2005
J Cell Biol (2005) 171 (4): 705–715.
Article history
Received:
April 04 2005
Accepted:
October 17 2005
Citation
Susanna C. Fagerholm, Tiina J. Hilden, Susanna M. Nurmi, Carl G. Gahmberg; Specific integrin α and β chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms . J Cell Biol 21 November 2005; 171 (4): 705–715. doi: https://doi.org/10.1083/jcb.200504016
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