Two Signals Are Necessary for Cell Proliferation Induced by a Cytokine Receptor gp130: Involvement of STAT3 in Anti-Apoptosis

Immunity. 1996 Nov;5(5):449-60. doi: 10.1016/s1074-7613(00)80501-4.

Abstract

gp130 is a common signal transducer for the interleukin-6-related cytokines. To delineate the gp130-mediated growth signal, we established a series of pro-B cell lines expressing chimeric receptors composed of the extracellular domain of the granulocyte colony-stimulating factor receptor and the transmembrane and cytoplasmic domains of gp130. The second tyrosine (from the membrane) of gp130, which was required for the tyrosine phosphorylation of SHP-2, its association with GRB2, and activation of a MAP kinase, was essential for mitogenesis, but not for anti-apoptosis. On the other hand, the tyrosine in the YXXQ motifs essential for STAT3 activation was required for bcl-2 induction and anti-apoptosis. Furthermore, dominant-negative STAT3 inhibited anti-apoptosis. These data demonstrate that two distinct signals, mitogenesis and anti-apoptosis, are required for gp130-induced cell growth and that STAT3 is involved in anti-apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / physiology*
  • Apoptosis / immunology*
  • Cell Division / immunology
  • Cell Line
  • Cytokine Receptor gp130
  • DNA-Binding Proteins / pharmacology*
  • Humans
  • Membrane Glycoproteins / physiology*
  • Mice
  • Proto-Oncogene Proteins c-myc / physiology
  • Recombinant Fusion Proteins / physiology
  • STAT3 Transcription Factor
  • Signal Transduction / immunology*
  • Trans-Activators / pharmacology*

Substances

  • Antigens, CD
  • DNA-Binding Proteins
  • IL6ST protein, human
  • Il6st protein, mouse
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • Trans-Activators
  • Cytokine Receptor gp130