Termination of IL-6-induced STAT activation is independent of receptor internalization but requires de novo protein synthesis

FEBS Lett. 2000 Mar 17;470(1):15-9. doi: 10.1016/s0014-5793(00)01276-x.

Abstract

The interleukin-6 (IL-6) receptor complex comprises the IL-6 receptor (IL-6R, gp80) and the signal transducer gp130. Binding of IL-6 to its receptor results in dimerization of gp130, activation of the Jak/STAT pathway, and in a down-regulation of IL-6 binding sites by endocytosis. The STAT activation after stimulation is transient, being maximal after 15-30 min and disappearing after 60-90 min. The mechanism which leads to the termination of the signal is still unknown. In this paper we have studied whether the down-modulation of the STAT signal requires the endocytosis of the receptor complex. Our results suggest that the desensitization of the IL-6 signal is not due to internalization of the receptor complex but requires de novo protein synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Cell Line
  • Cytokine Receptor gp130
  • DNA-Binding Proteins / metabolism*
  • Endocytosis*
  • Erythropoietin / metabolism
  • Humans
  • Interleukin-6 / metabolism*
  • Interleukin-6 / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / metabolism
  • Receptors, Interleukin-6 / metabolism*
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Trans-Activators / metabolism*
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • DNA-Binding Proteins
  • IL6ST protein, human
  • Il6st protein, mouse
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Receptors, Interleukin-6
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat1 protein, mouse
  • Stat3 protein, mouse
  • Trans-Activators
  • Erythropoietin
  • Cytokine Receptor gp130
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, mouse
  • Ptpn6 protein, mouse