No involvement of Erk/MAP kinases in IL-6-induced proliferation of a B cell hybridoma cell line.

Abstract

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.

• Authors: K Abe, K Mizuno, K Nakajima
• Journal: Osaka city medical journal (Osaka City Med J) Vol. 47 Issue 1 Pg. 63-72 (Jun 2001) ISSN: 0030-6096 [Print] Japan
• PMID: 11556393 (Publication Type: Journal Article)

Chemical References

• Interleukin-6
• Mitogen-Activated Protein Kinases

Topics

• B-Lymphocytes (drug effects, pathology)
• Cell Division (physiology)
• Cell Line
• Humans
• Hybridomas (cytology)
• Interleukin-6 (pharmacology)
• Mitogen-Activated Protein Kinases (physiology)