2 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 cyto kines. 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 s econd tyrosine (from the membrane) of gp130, which was required for th e tyrosine phosphorylation of SHP-2, its association with GRB2, and ac tivation of a MAP kinase, was essential for mitogenesis, but not for a nti-apoptosis. On the other hand, the tyrosine in the YXXQ motifs esse ntial for STAT3 activation was required for bcl-2 induction and anti-a poptosis. Furthermore, dominant-negative STAT3 inhibited anti-apoptosi s. These data demonstrate that two distinct signals, mitogenesis and a nti-apoptosis, are required for gp130-induced cell growth and that STA T3 is involved in anti-apoptosis.