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.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620837
Title:
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.
Authors:
Witte, Amelie; Meineke, Bernhard; Sticht, Jana; Philipsen, Lars; Kuropka, Benno; Müller, Andreas J; Freund, Christian; Schraven, Burkhart; Kliche, Stefanie
Abstract:
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
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.
Journal:
Molecular and cellular biology
Issue Date:
4-Jan-2017
URI:
http://hdl.handle.net/10033/620837
DOI:
10.1128/MCB.00509-16
PubMed ID:
28052935
Type:
Article
Language:
en
ISSN:
1098-5549
Appears in Collections:
publications of the research group intravital microscopy in infection and immunity (INMI)

Full metadata record

DC FieldValue Language
dc.contributor.authorWitte, Amelieen
dc.contributor.authorMeineke, Bernharden
dc.contributor.authorSticht, Janaen
dc.contributor.authorPhilipsen, Larsen
dc.contributor.authorKuropka, Bennoen
dc.contributor.authorMüller, Andreas Jen
dc.contributor.authorFreund, Christianen
dc.contributor.authorSchraven, Burkharten
dc.contributor.authorKliche, Stefanieen
dc.date.accessioned2017-02-22T15:22:27Z-
dc.date.available2017-02-22T15:22:27Z-
dc.date.issued2017-01-04-
dc.identifier.citationD120 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.en
dc.identifier.issn1098-5549-
dc.identifier.pmid28052935-
dc.identifier.doi10.1128/MCB.00509-16-
dc.identifier.urihttp://hdl.handle.net/10033/620837-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleD120 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.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalMolecular and cellular biologyen

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