Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of STAT3 in anti-apoptosis.
gp130 is a common signal transducer for the interleukin-6-related cytokines. To delineate the gp130-mediated growth signal, we established a series of pro-B cell lines expressing chimeric receptors composed of the extracellular domain of the granulocyte colony-stimulating factor receptor and the transmembrane and cytoplasmic domains of gp130. The second tyrosine (from the membrane) of gp130, which was required for the tyrosine phosphorylation of SHP-2, its association with GRB2, and activation of a MAP kinase, was essential for mitogenesis, but not for anti-apoptosis. On the other hand, the tyrosine in the YXXQ motifs essential for STAT3 activation was required for bcl-2 induction and anti-apoptosis. Furthermore, dominant-negative STAT3 inhibited anti-apoptosis. These data demonstrate that two distinct signals, mitogenesis and anti-apoptosis, are required for gp130-induced cell growth and that STAT3 is involved in anti-apoptosis.
Fukada
T
T
Department of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Japan.
Hibi
M
M
Yamanaka
Y
Y
Takahashi-Tezuka
M
M
Fujitani
Y
Y
Yamaguchi
T
T
Nakajima
K
K
Hirano
T
T
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000494:pharmacology*
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D008562:Membrane Glycoproteins; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D050822:Cytokine Receptor gp130