Cell type-specific roles of Jak3 in IL-2-induced proliferative signal transduction.
Binding of interleukin-2 (IL-2) to its specific receptor induces activation of two members of Jak family protein tyrosine kinases, Jak1 and Jak3. An IL-2 receptor (IL-2R)-reconstituted NIH 3T3 fibroblast cell line proliferates in response to IL-2 only when hematopoietic lineage-specific Jak3 is ectopically expressed. However, the mechanism of Jak3-dependent proliferation in the fibroblast cell line is not known. Here, I showed that Jak3 expression is dispensable for IL-2-induced activation of Jak1 and Stat proteins and expression of nuclear proto-oncogenes in the IL-2R-reconstituted fibroblast cell line. Jak3 expression markedly enhanced these IL-2-induced signaling events. In contrast, Jak3 expression was essential for induction of cyclin genes involved in the G1-S transition. These data suggest a critical role of Jak3 in IL-2 signaling in the fibroblast cell line and may provide further insight into the cell type-specific mechanism of cytokine signaling.
Fujii
Hodaka
H
Department of Pathology, New York University School of Medicine, 550 First Avenue, MSB-126, New York, NY 10016, USA. hodaka@med.nyu.edu
D000818:Animals; D001665:Binding Sites; D049109:Cell Proliferation; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology*; D016193:G1 Phase / Q000235:genetics / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology*; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism; D053616:Janus Kinase 3 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells / Q000166:cytology; D016196:S Phase / Q000235:genetics / Q000502:physiology; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D016213:Cyclins; D016207:Cytokines; D007376:Interleukin-2; D050791:STAT Transcription Factors; D053613:Janus Kinase 1; D053616:Janus Kinase 3