TGF-beta inhibits IL-2-induced tyrosine phosphorylation and activation of Jak-1 and Stat 5 in T lymphocytes.
Signaling through IL-2R, IL-2 induces tyrosine phosphorylation and activation of Jak-1 and Jak-3 kinases and Stat 3 and Stat 5 transcription factors leading to cell cycle progression of activated T cells from G1 to S phase. TGF-beta is an immunosuppressive cytokine, which inhibits T cell proliferation at G1 to S phase transition. We examined the effect of TGF-beta on IL-2R signal transduction pathway in activated T cells. We show here that treatment of activated T cells with TGF-beta inhibited IL-2-induced tyrosine phosphorylation and activation of Jak-1 and Stat 5 but not Jak-3 and Stat 3. TGF-beta also inhibited IL-2-induced expression of alpha- and beta-chains of IL-2R and induced apoptotic cell death in T cells. These results suggest that TGF-beta-induced growth arrest and apoptosis are associated with the modulation of IL-2-induced activation of Jak-Stat pathway in T cells.
Bright
J J
JJ
Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
Kerr
L D
LD
Sriram
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004336:Drug Antagonism; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology*; D053613:Janus Kinase 1; D051379:Mice; D008894:Milk Proteins; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1