Signal transduction of interleukin-6 involves tyrosine phosphorylation of multiple cytosolic proteins and activation of Src-family kinases Fyn, Hck, and Lyn in multiple myeloma cell lines

M. Hallek, C. Neumann, M. Schaffer, S. Danhauser-Riedl, N. Von Bubnoff, G. De Vos, B. J. Druker, K. Yasukawa, J. D. Griffin, B. Emmerich

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Abstract

Binding of interleukin-6 to its receptor (IL-6R) induces the association of the IL-6R α chain (IL-6Rα) with a 130-kDa transmembrane glycoprotein, gp130. This event activates tyrosine kinases of the Janus kinase (JAK) family and transduces signals to the cytosol or nucleus. To further characterize the biochemical mechanisms by which IL-6 promotes cell proliferation, we investigated the effects of IL-6 on the growth and transmembrane signaling of several lymphoid cell lines. In the IL-6-dependent cell line B-9, IL-6 induced a rapid, transient, and concentration-dependent tyrosine phosphorylation of several cytosolic proteins as detected by antiphosphotyrosine immunoblots. The molecular weight of major bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was 44, 65, 70, 80, 137, 148, 184, and 190 kDa, respectively. Similar effects of IL-6 on tyrosine phosphorylation were observed in the human multiple myeloma cell line LP-1. Because JAKs were unlikely to mediate all the biological effects of IL-6, we investigated whether members of the Src family of tyrosine kinases were also activated in B-9 or LP-1 cells. IL-6 induced the activation and tyrosine phosphorylation of p59(fyn), p56/59(Hck), and p56(Lyn). Coprecipitation experiments with anti-Hck, anti-Lyn, anti-Fyn, and anti-gp130 antibodies revealed a physical association with gp130 of p56/59(Hck) and p56(Lyn), but not p59(Fyn), in LP-1 cells. Together, these results show for the first time that several Src kinases may become activated by IL-6 (p59(Fyn), p56/59(Hck), and p56(Lyn)) and associate with gp130 (p56/59(Hck) and p56(Lyn)).

Original languageEnglish (US)
Pages (from-to)1367-1377
Number of pages11
JournalExperimental hematology
Volume25
Issue number13
StatePublished - Dec 1 1997

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Keywords

  • Cell signaling
  • Interleukin-6
  • Multiple myeloma
  • Src
  • Tyrosine kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

Cite this

Hallek, M., Neumann, C., Schaffer, M., Danhauser-Riedl, S., Von Bubnoff, N., De Vos, G., Druker, B. J., Yasukawa, K., Griffin, J. D., & Emmerich, B. (1997). Signal transduction of interleukin-6 involves tyrosine phosphorylation of multiple cytosolic proteins and activation of Src-family kinases Fyn, Hck, and Lyn in multiple myeloma cell lines. Experimental hematology, 25(13), 1367-1377.