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 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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| 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): | 26.08.2011 |
| Date of first Publication: | 26.08.2011 |
| Publishing Institution: | Univ.-Bibliothek Frankfurt am Main |
| Volume: | 286 |
| Issue: | 34 |
| Pagenumber: | 8 |
| First Page: | 29663 |
| Last Page: | 29670 |
| Institutes: | Medizin |
| Dewey Decimal Classification: | 570 Biowissenschaften; Biologie |
| 610 Medizin und Gesundheit | |
| Sammlungen: | Universitätspublikationen |
| Sondersammelgebiets-Volltexte Biologie | |
| 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 |
| Licence (German): |
