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Antiproliferative action of interferon-α requires components of T-cell-receptor signalling

Nature volume 390, pages 629–632 (1997)Cite this article

Abstract

Signal transduction through both cytokine and lymphocyte antigen receptors shares some common pathways by which they initiate cellular responses, such as activation of mitogen-activated protein kinase(s)1,2. However, other signalling components appear to be uniquely coupled to each receptor. For example, the interferon receptors transduce regulatory signals through the JAK/STAT pathway, resulting in an inhibition of growth and of antiviral effects, whereas this pathway apparently plays no role in T-cell-receptor (TCR)-dependent gene expression3,4. Conversely, signal transduction through the TCR requires the tyrosine kinases Lck and ZAP-70 and the tyrosine phosphatase CD45 (ref. 5). Here we show that, unexpectedly, transmission of growth-inhibitory signals by interferon-α (IFN-α) in T cells requires the expression and association of CD45, Lck and ZAP-70 with the IFN-α-receptor signalling complex.

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Figure 1: IFN-α-stimulates association of CD45, Lck and ZAP-70 with the IFN-α receptor (IFNaR1) and ligand-induced tyrosine-phosphorylation of ZAP-70.
Figure 2: IFN-α-stimulated inhibition of cell growth is absent in Jurkat cells which do not express CD45, Lck or ZAP-70.
Figure 3: IFN-α-induced activation of the JAK/STAT pathway is identical in wild-type (WT) and variant Jurkat cells.
Figure 4: IFN-α-stimulated association of CD45, Lck and ZAP-70 with IFNaR1 in Jurkat cells.
Figure 5: Representation of the distinct biological effects mediated by IFN-α in T cells.

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Acknowledgements

We thank S. Goelz and C. Benjamin for antibodies against IFNaR1.

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Author notes

  1. Andrew C. Larner

    Present address: Department of Medicine and Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, 94143, California, USA

  2. Ana Gamero

    Present address: Department of Immunology, Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, 44195, USA

Authors and Affiliations

  1. Center for Biologics, Evaluation and Research, FDA, Bethesda, 20892, Maryland, USA

    Emanuel F. Petricoin III, Satoshi Ito, Susette Audet, Louis F. Stancato, Kathleen Clouse, Judy Beeler, David S. Finbloom, Elizabeth W. Shores & Andrew C. Larner

  2. Department of Immunology and Pharmacology, Mayo Clinic, Rochester, 55905, Minnesota, USA

    Brandi L. Williams & Robert Abraham

  3. Department of Pathology, USUHS, Jones Bridge Rd, Bethesda, 20892, Maryland, USA

    Philip Grimley

  4. Department of Medicine and Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, 94143, California, USA

    Arthur Weiss

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Correspondence to Andrew C. Larner.

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Petricoin, E., Ito, S., Williams, B. et al. Antiproliferative action of interferon-α requires components of T-cell-receptor signalling. Nature 390, 629–632 (1997). https://doi.org/10.1038/37648

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