i)Two
Signals Are Necessary for Cell Proliferation Induced by a Cytokine
Receptor gp130: Involvement of STAT3 in Anti-Apoptosis.i)Two
Signals Are Necessary for Cell Proliferation Induced by a Cytokine
Receptor gp130: Involvement of STAT3 in Anti-Apoptosis.
Toshiyuki Fukada, Masahiko Hibi, Yojiro Yamanaka, Mariko
Takahashi-Tezuka, Yoshio Fujitani, Takuya Yamaguchi, Koichi
Nakajima,
and Toshio Hirano, Immunity, Vol. 5, 449-460, 1996 (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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