Cutting edge: role of STAT1, STAT3, and STAT5 in IFN-alpha beta responses in T lymphocytes.
Engagement of the IFN-alphabeta receptor initiates multiple signaling cascades, including activation of the STAT. In this study, we demonstrate that IFN-alphabeta, although antiproliferative in wild-type CD4(+) or CD8(+) T cells, act as strong mitogens on their STAT1(-/-) counterparts. Furthermore, IFN-alphabeta exert little effect on apoptosis in wild-type cells, but are potent survival factors in the absence of STAT1. The antiapoptotic response in the absence of STAT1 is predominantly mediated by STAT3, and to a lesser extent by STAT5A/B. In contrast, the mitogenic IFN-alphabeta response gained through the absence of STAT1 is only marginally affected when STAT5A/B expression is also abrogated, but is completely dependent on STAT3 activation. These findings provide the first evidence for a function of STAT3 and STAT5A/B in the IFN-alphabeta response, and support a model in which the IFN-alphabeta receptor initiates both pro- and antiapoptotic responses through STAT1, and STAT3 and STAT5A/B, respectively.
Tanabe
Yoshinari
Y
Division of Biological Sciences, and Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Nishibori
Takeaki
T
Su
Leon
L
Arduini
Robert M
RM
Baker
Darren P
DP
David
Michael
M
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006131:Growth Inhibitors / Q000494:pharmacology / Q000502:physiology; D007370:Interferon Type I / Q000494:pharmacology / Q000502:physiology*; D016898:Interferon-alpha / Q000502:physiology; D016899:Interferon-beta / Q000494:pharmacology / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins / Q000235:genetics; D008934:Mitogens / Q000494:pharmacology / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D007370:Interferon Type I; D016898:Interferon-alpha; D008894:Milk Proteins; D008934:Mitogens; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; C494093:Stat5a protein, mouse; D015534:Trans-Activators; D016899:Interferon-beta