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Mol Cell Biol. 2017 Mar 17;37(7). pii: e00509-16. doi: 10.1128/MCB.00509-16. Print 2017 Apr 1.

D120 and K152 within the PH Domain of T Cell Adapter SKAP55 Regulate Plasma Membrane Targeting of SKAP55 and LFA-1 Affinity Modulation in Human T Lymphocytes.

Author information

1
Otto von Guericke University, Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation, Magdeburg, Germany.
2
Freie Universität Berlin, Institut für Chemie und Biochemie, Protein Biochemistry Group, Berlin, Germany.
3
Helmholtz Center for Infection Research (HZI), Department of Immune Control, Braunschweig, Germany.
4
Otto von Guericke University, Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation, Magdeburg, Germany burkhart.schraven@med.ovgu.de stefanie.kliche@med.ovgu.de.

Abstract

The β2-integrin lymphocyte function-associated antigen 1 (LFA-1) is needed for the T cell receptor (TCR)-induced activation of LFA-1 to promote T cell adhesion and interaction with antigen-presenting cells (APCs). LFA-1-mediated cell-cell interactions are critical for proper T cell differentiation and proliferation. The Src kinase-associated phosphoprotein of 55 kDa (SKAP55) is a key regulator of TCR-mediated LFA-1 signaling (inside-out/outside-in signaling). To gain an understanding of how SKAP55 controls TCR-mediated LFA-1 activation, we assessed the functional role of its pleckstrin homology (PH) domain. We identified two critical amino acid residues within the PH domain of SKAP55, aspartic acid 120 (D120) and lysine 152 (K152). D120 facilitates the retention of SKAP55 in the cytoplasm of nonstimulated T cells, while K152 promotes SKAP55 membrane recruitment via actin binding upon TCR triggering. Importantly, the K152-dependent interaction of the PH domain with actin promotes the binding of talin to LFA-1, thus facilitating LFA-1 activation. These data suggest that K152 and D120 within the PH domain of SKAP55 regulate plasma membrane targeting and TCR-mediated activation of LFA-1.

KEYWORDS:

LFA-1; SKAP55; adhesion

PMID:
28052935
PMCID:
PMC5359422
DOI:
10.1128/MCB.00509-16
[Indexed for MEDLINE]
Free PMC Article

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