TY  - JOUR
A1  - Raab, Monika
A1  - Smith, Xin
A1  - Matthess, Yves
A1  - Strebhardt, Klaus
A1  - Rudd, Christopher E.
T1  - SKAP1 protein PH domain determines RapL membrane localization and Rap1 protein complex formation for T cell receptor (TCR) activation of LFA-1
T2  - The journal of biological chemistry
N2  - 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.
KW  - Cell Adhesion
KW  - Immunology
KW  - Integrin
KW  - Lymphocyte
KW  - PI3K
KW  - Protein Translocation
KW  - LFA-1
KW  - SKAP1
KW  - T Cells
KW  - Inside-out Signaling
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/25543
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-255436
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191007/
SN  - 0021-9258
SN  - 1083-351X
N1  - © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
VL  - 286
IS  - 34
SP  - 29663
EP  - 29670
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda, Md.
ER  -