title: Guanylate binding protein 1-mediated interaction of T cell antigen receptor signaling with the cytoskeleton.
abstract: GTPases act as important switches in many signaling events in cells. Although small and heterotrimeric G proteins are subjects of intensive studies, little is known about the large IFN-inducible GTPases. In this article, we show that the IFN-γ-inducible guanylate binding protein 1 (GBP-1) is a regulator of T cell activation. Silencing of GBP-1 leads to enhanced activation of early T cell Ag receptor/CD3 signaling molecules, including Lck, that is translated to higher IL-2 production. Mass spectrometry analyses showed that regulatory cytoskeletal proteins, like plastin-2 that bundles actin fibers and spectrin β-chain, brain 1 that links the plasma membrane to the actin cytoskeleton, are binding partners of GBP-1. The spectrin cytoskeleton influences cell spreading and surface expression of TCR/CD3 and the leukocyte phosphatase CD45. We found higher cell spreading and enhanced surface expression of TCR/CD3 and CD45 in GBP-1 silenced T cells that explain their enhanced TCR/CD3 signaling. We conclude that GBP-1 is a downstream processor of IFN-γ via which T cells regulate cytoskeleton-dependent cell functions.
authors: Molecular Immunology Unit, Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria;
authors: Florian
authors: F
authors: Forster
authors: Wolfgang
authors: W
authors: Paster
authors: Verena
authors: V
authors: Supper
authors: Philipp
authors: P
authors: Schatzlmaier
authors: Stefan
authors: S
authors: Sunzenauer
authors: Nicole
authors: N
authors: Ostler
authors: Anna
authors: A
authors: Saliba
authors: Paul
authors: P
authors: Eckerstorfer
authors: Nathalie
authors: N
authors: Britzen-Laurent
authors: Gerhard
authors: G
authors: Schütz
authors: Johannes A
authors: JA
authors: Schmid
authors: Gerhard J
authors: GJ
authors: Zlabinger
authors: Elisabeth
authors: E
authors: Naschberger
authors: Michael
authors: M
authors: Stürzl
authors: Hannes
authors: H
authors: Stockinger
mesh_terms: D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens; D007962:Leukocytes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D017252:CD3 Complex; C490287:GBP1 protein, human; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; C026742:plastin; D007371:Interferon-gamma; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D019204:GTP-Binding Proteins