No involvement of Erk/MAP kinases in IL-6-induced proliferation of a B cell hybridoma cell line.
Interleukin-6 (IL-6) is a pleiotropic cytokine and acts as a growth factor for murine plasmacytoma and human myeloma. IL-6 activates multiple signal transduction pathways. Among them, signal transducer and activator of transcription3 (STAT3), and the SHP-2-mediated Erk/MAP kinase pathway are important. The roles for the two major pathways in the IL-6-induced growth of B cell hybridoma cells were examined. A mutational analysis of the cytoplasmic domain of exogenously expressed gp130, a signal transducing beta chain of the IL-6 receptor complex, revealed that the proximal 133 amino acid (AA) region of gp130 with the intact Y767 but not Y759 is necessary and sufficient for gp130-signal-induced cell proliferation. Interestingly, no requirement of the Y759-mediated signals, including SHP-2-mediated Erk/MAP kinase pathway, coincided with the failure of SHP-2, Gab1/Gab2, and Erk/MAP kinase activation by IL-6 in MH60 cells. Moreover, we show that another serine/threonine kinase pathway leading to STAT3 Ser727 phosphorylation, which seemed to be derived from the Y767 in the proximal 133 AA residues, is intact in MH60 cells. Since Erk/MAP kinases are known to inhibit the subsequent IL-6-induced STAT3 activation, the impaired activation of Erk/MAP kinases by IL-6 may contribute to the development of B cell neoplasia.
Abe
K
K
Department of Immunology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Mizuno
K
K
Nakajima
K
K
D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D006801:Humans; D006825:Hybridomas / Q000166:cytology*; D015850:Interleukin-6 / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*
D015850:Interleukin-6; D020928:Mitogen-Activated Protein Kinases