Predominant expression of the long isoform of GP130-like (GPL) receptor is required for interleukin-31 signaling

Eur Cytokine Netw. 2004 Oct-Dec;15(4):291-302.

Abstract

Gp130-like receptor (GPL) is a newly identified cytokine receptor. A recent study reported the involvement of GPL, together with OSMR, in the formation of the receptor complex for IL-31, a novel immune cytokine with a skin tropism. In the present work, we analyzed the signaling properties of IL-31 in glioblastoma and melanoma tumor cells. We demonstrate that in response to IL-31, its receptor complex recruits Jak1, Jak2, STAT1, -3, -5 signaling pathways, as well as the Pi3 kinase / AKT cascade. SHP-2 and Shc adapter molecules are also recruited and contribute to an increased activation of the MAP kinase pathway in response to IL-31. Different responses were observed depending on the expression of short or long GPL receptor isoform within the studied cell lines. We show that the short form of GPL receptor exerts a profound inhibitory effect on the signaling of IL-31 and behaves as a dominant negative receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Line, Tumor
  • Cricetinae
  • Gene Expression Regulation / immunology*
  • Humans
  • Interleukins / immunology*
  • Protein Isoforms / immunology
  • Receptors, Cytokine / immunology*
  • Receptors, Interleukin / immunology*
  • Signal Transduction / immunology*

Substances

  • IL31 protein, human
  • IL31RA protein, human
  • Interleukins
  • Protein Isoforms
  • Receptors, Cytokine
  • Receptors, Interleukin
  • cytokine receptor, GLM-R