[HTML][HTML] Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of STAT3 in anti-apoptosis

T Fukada, M Hibi, Y Yamanaka, M Takahashi-Tezuka… - Immunity, 1996 - cell.com
T Fukada, M Hibi, Y Yamanaka, M Takahashi-Tezuka, Y Fujitani, T Yamaguchi, K Nakajima…
Immunity, 1996cell.com
Abstract 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 …
Abstract
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.
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