Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells

Yun Qiu, Lakshmeswari Ravi and Hsing-Jien Kung ()
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Yun Qiu: Case Western Reserve University, School of Medicine
Lakshmeswari Ravi: Case Western Reserve University, School of Medicine
Hsing-Jien Kung: Case Western Reserve University, School of Medicine

Nature, 1998, vol. 393, issue 6680, 83-85

Abstract: 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.

Date: 1998
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DOI: 10.1038/30012

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