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PMID: 16301335 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Specific integrin alpha and beta chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms.

The Journal of cell biology ·Vol. 171 ·No. 4 ·2005-11-21 ·Pages 705-15

Fagerholm SC, Hilden TJ, Nurmi SM, Gahmberg CG

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. alpha 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 beta 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.

MeSH Terms
14-3-3 Proteins/metabolism Amino Acid Sequence Animals Antigens, CD/metabolism COS Cells Cell Adhesion Cell Adhesion Molecules/metabolism Cell Line Cell Line, Tumor Chemokines/metabolism Chlorocebus aethiops Chromatography, Affinity Cytoplasm/metabolism Cytoskeleton/metabolism DNA, Complementary/metabolism Electrophoresis, Polyacrylamide Gel Flow Cytometry Humans Immunoprecipitation Integrins/metabolism Intercellular Adhesion Molecule-1/metabolism Lymphocyte Function-Associated Antigen-1/physiology Microscopy, Fluorescence Molecular Sequence Data Mutation Phosphorylation Protein Binding Protein Conformation Protein Structure, Tertiary Proteins/metabolism Recombinant Proteins/chemistry Serine/chemistry Talin/chemistry Time Factors Transfection
Chemicals
14-3-3 Proteins Antigens, CD Cell Adhesion Molecules Chemokines DNA, Complementary ICAM2 protein, human Integrins Lymphocyte Function-Associated Antigen-1 Proteins Recombinant Proteins SDF2 protein, human Talin Intercellular Adhesion Molecule-1 Serine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Fagerholm Susanna C
Division of Biochemistry, Faculty of Biosciences, University of Helsinki, FIN-00014 Helsinki, Finland.
Hilden Tiina J
Nurmi Susanna M
Gahmberg Carl G
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200504016
Published
2005-11-21
Pages
705-15
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171568
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200504016 PMC Full Text View journal details
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