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

Nature. 1998 May 7;393(6680):83-5. doi: 10.1038/30012.

Abstract

Interleukin-6 (IL-6) is a cytokine that was initially recognized as a regulator of immune and inflammatory responses, but it also regulates the growth of many tumour cells, including prostrate carcinoma. Overexpression of the growth-factor receptors ErbB2/neu and ErbB3 has been implicated in the neoplastic transformation of prostate carcinoma. 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Enzyme Activation
  • ErbB Receptors / metabolism
  • Humans
  • Interleukin-6 / metabolism*
  • Male
  • Phosphorylation
  • Prostate / metabolism*
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Receptor, ErbB-2 / physiology*
  • Receptor, ErbB-3
  • Shc Signaling Adaptor Proteins
  • Signal Transduction*
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Tumor Cells, Cultured
  • Tyrosine / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Interleukin-6
  • Proteins
  • Proto-Oncogene Proteins
  • SHC1 protein, human
  • Shc Signaling Adaptor Proteins
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Tyrosine
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Calcium-Calmodulin-Dependent Protein Kinases