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

被引:570
作者
Fukada, T [1 ]
Hibi, M [1 ]
Yamanaka, Y [1 ]
TakahashiTezuka, M [1 ]
Fujitani, Y [1 ]
Yamaguchi, T [1 ]
Nakajima, K [1 ]
Hirano, T [1 ]
机构
[1] OSAKA UNIV,SCH MED,BIOMED RES CTR,DEPT MOL ONCOL,SUITA,OSAKA 565,JAPAN
关键词
D O I
10.1016/S1074-7613(00)80501-4
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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页码:449 / 460
页数:12
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