Filamin A Phosphorylation at Serine 2152 by the Serine/Threonine Kinase Ndr2 Controls TCR-Induced LFA-1 Activation in T Cells.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Demiray, Yunus Emre
Turk, Benjamin E
Müller, Andreas J
MetadataShow full item record
AbstractThe integrin LFA-1 (CD11a/CD18) plays a critical role in the interaction of T cells with antigen presenting cells (APCs) to promote lymphocyte differentiation and proliferation. This integrin can be present either in a closed or in an open active conformation and its activation upon T-cell receptor (TCR) stimulation is a critical step to allow interaction with APCs. In this study we demonstrate that the serine/threonine kinase Ndr2 is critically involved in the initiation of TCR-mediated LFA-1 activation (open conformation) in T cells. Ndr2 itself becomes activated upon TCR stimulation and phosphorylates the intracellular integrin binding partner Filamin A (FLNa) at serine 2152. This phosphorylation promotes the dissociation of FLNa from LFA-1, allowing for a subsequent association of Talin and Kindlin-3 which both stabilize the open conformation of LFA-1. Our data suggest that Ndr2 activation is a crucial step to initiate TCR-mediated LFA-1 activation in T cells.
CitationFront Immunol. 2018 Dec 4;9:2852. doi: 10.3389/fimmu.2018.02852. eCollection 2018.
AffiliationHZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig Germany.
JournalFrontiers in immunology
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Talin1 regulates TCR-mediated LFA-1 function.
- Authors: Simonson WT, Franco SJ, Huttenlocher A
- Issue date: 2006 Dec 1
- Kindlin-3 is required for the stabilization of TCR-stimulated LFA-1:ICAM-1 bonds critical for lymphocyte arrest and spreading on dendritic cells.
- Authors: Feigelson SW, Grabovsky V, Manevich-Mendelson E, Pasvolsky R, Shulman Z, Shinder V, Klein E, Etzioni A, Aker M, Alon R
- Issue date: 2011 Jun 30
- 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 A, Meineke B, Sticht J, Philipsen L, Kuropka B, Müller AJ, Freund C, Schraven B, Kliche S
- Issue date: 2017 Apr 1
- Beta2-integrin, LFA-1, and TCR/CD3 synergistically induce tyrosine phosphorylation of focal adhesion kinase (pp125(FAK)) in PHA-activated T cells.
- Authors: Tabassam FH, Umehara H, Huang JY, Gouda S, Kono T, Okazaki T, van Seventer JM, Domae N
- Issue date: 1999 May 1
- A novel intracellular pool of LFA-1 is critical for asymmetric CD8<sup>+</sup> T cell activation and differentiation.
- Authors: Capece T, Walling BL, Lim K, Kim KD, Bae S, Chung HL, Topham DJ, Kim M
- Issue date: 2017 Nov 6