Fagerholm, SC

Gahmberg, CG

Hilden, TJ

Nurmi, SM

English

PubMed

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. a 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 ß 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. © 2005 Fagerholm et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). </p

Fagerholm, Susanna C.

Hilden, Tiina J.

Nurmi, Susanna M.

Gahmberg, Carl G.

University of Dundee Online Publications

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

Discovery Research Portal

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

Helsingin yliopiston digitaalinen arkisto

Susanna C. Fagerholm

Tiina J. Hilden

Susanna M. Nurmi

Carl G. Gahmberg

Crossref

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

14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation.

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Rap1 functions as a key regulator of T-cell and antigen-presenting cell interactions and modulates T-cell responses.

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The cytoskeletal association of CD11/CD18 leukocyte integrins in phorbol ester-activated T cells correlates with CD18 phosphorylation.

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(CD18) integrin phosphorylation in phorbol ester-activated T lymphocytes.

key regulator of T-cell and antigen-presenting cell interactions and modulates T-cell responses.

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Spatial restriction of 4 integrin phosphorylation regulates lamellipodial stability and 4 1-dependent cell migration.

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The primacy of affinity over clustering in regulation of adhesiveness of the integrin L 2.

The small GTPase Rap1 is required for Mn2 - and antibodyinduced LFA-1 and VLA-4-mediated cell adhesion.

Three-dimensional EM structure of the ectodomain of integrin V 3 in a complex with fibronectin.

https://discovery.dundee.ac.uk/files/732481/Fagerholm_2005.pdf

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

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University of Dundee Online Publications

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Helsingin yliopiston digitaalinen arkisto

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Helsingin yliopiston digitaalinen arkisto

University of Dundee Online Publications