SKAP1 protein PH domain determines RapL membrane localization and Rap1 protein complex formation for T cell receptor (TCR) activation of LFA-1

Although essential for T cell function, the identity of the T cell receptor (TCR) “inside-out” pathway for the activation of lymphocyte function-associated antigen 1 (LFA-1) is unclear. SKAP1 (SKAP-55) is the upstream re
Although essential for T cell function, the identity of the T cell receptor (TCR) “inside-out” pathway for the activation of lymphocyte function-associated antigen 1 (LFA-1) is unclear. SKAP1 (SKAP-55) is the upstream regulator needed for TCR-induced RapL-Rap1 complex formation and LFA-1 activation. In this paper, we show that SKAP1 is needed for RapL binding to membranes in a manner dependent on the PH domain of SKAP1 and the PI3K pathway. A SKAP1 PH domain-inactivating mutation (i.e. R131M) markedly impaired RapL translocation to membranes for Rap1 and LFA-1 binding and the up-regulation of LFA-1-intercellular adhesion molecule 1 (ICAM-1) binding. Further, N-terminal myr-tagged SKAP1 for membrane binding facilitated constitutive RapL membrane and Rap1 binding and effectively substituted for PI3K and TCR ligation in the activation of LFA-1 in T cells.
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Metadaten
Author:Monika Raab, Xin Smith, Yves Matthess, Klaus Strebhardt, Christopher E. Rudd
URN:urn:nbn:de:hebis:30:3-255436
DOI:http://dx.doi.org/10.1074/jbc.M111.222661
ISSN:0021-9258
ISSN:1083-351X
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=21669874
Parent Title (English):The journal of biological chemistry
Publisher:American Society for Biochemistry and Molecular Biology
Place of publication:Bethesda, Md.
Document Type:Article
Language:English
Date of Publication (online):2011/08/26
Date of first Publication:2011/08/26
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2012/07/16
Volume:286
Issue:34
Pagenumber:8
First Page:29663
Last Page:29670
Note:
Author's Choice—Final version full access. http://creativecommons.org/licenses/by-nc/3.0/ Creative Commons Attribution Non-Commercial License applies to Author Choice Articles 
Institutes:Medizin
Dewey Decimal Classification:570 Biowissenschaften; Biologie
610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0

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