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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CD3 Complex / genetics
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CD3 Complex / metabolism
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Cell Line
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Cell Line, Tumor
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Cytoskeleton / genetics
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Cytoskeleton / metabolism*
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Cytosol / metabolism
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism*
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HEK293 Cells
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Humans
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Interferon-gamma / genetics
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Interferon-gamma / metabolism
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Interleukin-2 / genetics
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Interleukin-2 / metabolism
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Jurkat Cells
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Leukocyte Common Antigens
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Leukocytes / metabolism
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Lymphocyte Activation / genetics
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism
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Receptor-CD3 Complex, Antigen, T-Cell / genetics
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Receptor-CD3 Complex, Antigen, T-Cell / metabolism*
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / metabolism*
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Signal Transduction / genetics
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T-Lymphocytes / metabolism
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Up-Regulation / genetics
Substances
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CD3 Complex
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GBP1 protein, human
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Interleukin-2
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Membrane Glycoproteins
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Microfilament Proteins
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Receptor-CD3 Complex, Antigen, T-Cell
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Receptors, Antigen, T-Cell
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plastin
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Interferon-gamma
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Leukocyte Common Antigens
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PTPRC protein, human
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GTP-Binding Proteins