Antiproliferative action of interferon-alpha requires components of T-cell-receptor signalling.
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.
Petricoin
E F
EF
Center for Biologics, Evaluation and Research, FDA, Bethesda, Maryland 20892, USA.
Ito
S
S
Williams
B L
BL
Audet
S
S
Stancato
L F
LF
Gamero
A
A
Clouse
K
K
Grimley
P
P
Weiss
A
A
Beeler
J
J
Finbloom
D S
DS
Shores
E W
EW
Abraham
R
R
Larner
A C
AC
D000818:Animals; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000378:metabolism / Q000502:physiology*; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008459:Measles virus / Q000187:drug effects / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D017471:Receptors, Interferon / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects; D051746:ZAP-70 Protein-Tyrosine Kinase
D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D016898:Interferon-alpha; D011948:Receptors, Antigen, T-Cell; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D015534:Trans-Activators; D053633:Receptor, Interferon alpha-beta; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D017493:Leukocyte Common Antigens