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Front Immunol. 2018 Dec 4;9:2852. doi: 10.3389/fimmu.2018.02852. eCollection 2018.

Filamin A Phosphorylation at Serine 2152 by the Serine/Threonine Kinase Ndr2 Controls TCR-Induced LFA-1 Activation in T Cells.

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Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University, Magdeburg, Germany.
Institute of Biology, Department of Genetics and Molecular Neurobiology, Otto-von-Guericke University, Magdeburg, Germany.
MD Anderson Cancer Center, University of Texas, Houston, TX, United States.
Department of Pharmacology, Yale School of Medicine, New Haven, CT, United States.
Protein Biochemistry Group, Institut für Chemie und Biochemie, Freie Universität Berlin, Berlin, Germany.
Intravital Microscopy of Infection and Immunity, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Department of Immune Control Helmholtz Center for Infection Research, Braunschweig, Germany.
Center for Behavioral Brain Sciences, Magdeburg, Germany.


The 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.


Filamin A; Kindlin-3; LFA-1; Ndr2; T cells; TCR; Talin; inside-out signaling

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