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

E. F. Petricoin; S. Ito; B. L. Williams; S. Audet; L. F. Stancato; A. Gamero; K. Clouse; P. Grimley; A. Weiss; J. Beeler; D. S. Finbloom; E. W. Shores; R. Abraham; A. C. Larner

doi:10.1038/37648

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

E. F. Petricoin, S. Ito, B. L. Williams, S. Audet, L. F. Stancato, A. Gamero, K. Clouse, P. Grimley, A. Weiss, J. Beeler, D. S. Finbloom, E. W. Shores, R. Abraham, A. C. Larner

United States Food and Drug Administration

Research output: Contribution to journal › Article › peer-review

141 Scopus citations

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). 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 expression. 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.

Original language	English
Pages (from-to)	629-632
Number of pages	4
Journal	Nature
Volume	390
Issue number	6660
DOIs	https://doi.org/10.1038/37648
State	Published - 1997

Keywords

Animals
Chlorocebus aethiops
DNA-Binding Proteins/metabolism
Growth Inhibitors/metabolism
Humans
In Vitro Techniques
Interferon-alpha/metabolism
Jurkat Cells
Leukocyte Common Antigens/metabolism
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism
Measles virus/drug effects
Protein-Tyrosine Kinases/metabolism
Receptor, Interferon alpha-beta
Receptors, Antigen, T-Cell/metabolism
Receptors, Interferon/metabolism
STAT1 Transcription Factor
STAT2 Transcription Factor
Signal Transduction
Trans-Activators/metabolism
Vero Cells
Virus Replication/drug effects
ZAP-70 Protein-Tyrosine Kinase

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title = "Antiproliferative action of interferon-α requires components of T- cell-receptor signalling",

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). 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 expression. 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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author = "Petricoin, {E. F.} and S. Ito and Williams, {B. L.} and S. Audet and Stancato, {L. F.} and A. Gamero and K. Clouse and P. Grimley and A. Weiss and J. Beeler and Finbloom, {D. S.} and Shores, {E. W.} and R. Abraham and Larner, {A. C.}",

year = "1997",

doi = "10.1038/37648",

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AU - Petricoin, E. F.

AU - Ito, S.

AU - Williams, B. L.

AU - Audet, S.

AU - Stancato, L. F.

AU - Gamero, A.

AU - Clouse, K.

AU - Grimley, P.

AU - Weiss, A.

AU - Beeler, J.

AU - Finbloom, D. S.

AU - Shores, E. W.

AU - Abraham, R.

AU - Larner, A. C.

PY - 1997

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N2 - 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). 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 expression. 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.

AB - 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). 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 expression. 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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Antiproliferative action of interferon-α requires components of T- cell-receptor signalling

Abstract

Keywords

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