Abstract
Interleukin-6 (IL-6) is a cytokine that was initially recognized as a regulator of immune and inflammatory responses1, but it also regulates the growth of many tumour cells, including prostrate carcinoma2,3,4. Overexpression of the growth-factor receptors ErbB2/neu and ErbB3 has been implicated in the neoplastic transformation of prostate carcinoma5,6,7. Here we show that treatment of the prostate cancer cell line LNCaP with IL-6 induces tyrosine phosphorylation of ErbB2 and ErbB3, but not ErbB1/EGFR. We also show that ErbB2 forms a complex with the gp130 subunit of the IL-6 receptor in an IL-6-dependent manner. This association is important because the inhibition of ErbB2 activity results in abrogation of IL-6-induced MAPK activation. Thus ErbB2 is a critical component of IL-6 signalling through the MAP kinase pathway. These data show how a cytokine receptor can diversify its signalling pathways by engaging with a growth-factor receptor kinase.
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Acknowledgements
We thank N. E. Hynes for the scFv5R clone, J. Jacobberger and T. G. Pretlow for CWR22 cells, and A. W. Grasso and K. Everiss for reading the manuscript. This work was supported by NIH grants. Y.Q. is a recipient of an NCI research oncology training fellowship.
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Qiu, Y., Ravi, L. & Kung, HJ. Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells. Nature 393, 83–85 (1998). https://doi.org/10.1038/30012
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DOI: https://doi.org/10.1038/30012
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