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

E F Petricoin 3rd; 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-alpha requires components of T-cell-receptor signalling

Nature. 1997 Dec 11;390(6660):629-32. doi: 10.1038/37648.

Authors

E F Petricoin 3rd¹, 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

Affiliation

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

PMID: 9403695
DOI: 10.1038/37648

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. Here we show that, unexpectedly, transmission of growth-inhibitory signals by interferon-alpha (IFN-alpha) in T cells requires the expression and association of CD45, Lck and ZAP-70 with the IFN-alpha-receptor signalling complex.

MeSH terms

Animals
Chlorocebus aethiops
DNA-Binding Proteins / metabolism
Growth Inhibitors / metabolism
Growth Inhibitors / physiology*
Humans
In Vitro Techniques
Interferon-alpha / metabolism
Interferon-alpha / physiology*
Jurkat Cells
Leukocyte Common Antigens / metabolism
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
Measles virus / drug effects
Measles virus / physiology
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

Substances

DNA-Binding Proteins
Growth Inhibitors
Interferon-alpha
Receptors, Antigen, T-Cell
Receptors, Interferon
STAT1 Transcription Factor
STAT1 protein, human
STAT2 Transcription Factor
Trans-Activators
Receptor, Interferon alpha-beta
Protein-Tyrosine Kinases
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
ZAP-70 Protein-Tyrosine Kinase
ZAP70 protein, human
Leukocyte Common Antigens