Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4.
Interleukin 12 (IL-12) initiates the differentiation of naive CD4+ T cells to T helper type 1 (Th1) cells critical for resistance to intracellular pathogens such as Leishmania major. To explore the basis of IL-12 action, we analyzed induction of nuclear factors in Th1 cells. IL-12 selectively induced nuclear DNA-binding complexes that contained Stat3 and Stat4, recently cloned members of the family of signal transducers and activators of transcription (STATs). While Stat3 participates in signaling for several other cytokines, Stat4 was not previously known to participate in the signaling pathway for any natural ligand. The selective activation of Stat4 provides a basis for unique actions of IL-12 on Th1 development. Thus, this study presents the first identification of the early events in IL-12 signaling in T cells and of ligand activation of Stat4.
Jacobson
N G
NG
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Szabo
S J
SJ
Weber-Nordt
R M
RM
Zhong
Z
Z
Schreiber
R D
RD
Darnell
J E
JE
Murphy
K M
KM
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D015398:Signal Transduction; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; C494087:Stat3 protein, mouse; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D014443:Tyrosine; D007371:Interferon-gamma; D004247:DNA