Guanylate binding protein 1-mediated interaction of T cell antigen receptor signaling with the cytoskeleton

J Immunol. 2014 Jan 15;192(2):771-81. doi: 10.4049/jimmunol.1300377. Epub 2013 Dec 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD3 Complex / genetics
  • CD3 Complex / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cytoskeleton / genetics
  • Cytoskeleton / metabolism*
  • Cytosol / metabolism
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Jurkat Cells
  • Leukocyte Common Antigens
  • Leukocytes / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Receptor-CD3 Complex, Antigen, T-Cell / genetics
  • Receptor-CD3 Complex, Antigen, T-Cell / metabolism*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction / genetics
  • T-Lymphocytes / metabolism
  • Up-Regulation / genetics


  • CD3 Complex
  • GBP1 protein, human
  • Interleukin-2
  • Membrane Glycoproteins
  • Microfilament Proteins
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Receptors, Antigen, T-Cell
  • plastin
  • Interferon-gamma
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Leukocyte Common Antigens
  • PTPRC protein, human
  • GTP-Binding Proteins