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.
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Authors
Witte, AmelieMeineke, Bernhard
Sticht, Jana
Philipsen, Lars
Kuropka, Benno
Müller, Andreas J
Freund, Christian
Schraven, Burkhart
Kliche, Stefanie
Issue Date
2017-01-04
Metadata
Show full item recordAbstract
The β2-integrin lymphocyte function-associated antigen-1 (LFA-1) is needed for 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 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 retention of SKAP55 in the cytoplasm of non-stimulated 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.Citation
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. 2017 Mol. Cell. Biol.Affiliation
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.Journal
Molecular and cellular biologyPubMed ID
28052935Type
ArticleLanguage
enISSN
1098-5549ae974a485f413a2113503eed53cd6c53
10.1128/MCB.00509-16
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
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