Roles of STAT3 in Mediating the Cell Growth, Differentiation and Survival Signals Relayed Through the IL-6 Family of Cytokine Receptors

Oncogene. 2000 May 15;19(21):2548-56. doi: 10.1038/sj.onc.1203551.

Abstract

Members of the IL-6 cytokine family are involved in a variety of biological responses, including the immune response, inflammation, hematopoiesis, and oncogenesis by regulating cell growth, survival, and differentiation. These cytokines use gp130 as a common receptor subunit. The binding of ligand to gp130 activates the JAK/STAT signal transduction pathway, where STAT3 plays a central role in transmitting the signals from the membrane to the nucleus. STAT3 is essential for gp130-mediated cell survival and G1 to S cell-cycle-transition signals. Both c-myc and pim have been identified as target genes of STAT3 and together can compensate for STAT3 in cell survival and cell-cycle transition. STAT3 is also required for gp130-mediated maintenance of the pluripotential state of proliferating embryonic stem cells and for the gp130-induced macrophage differentiation of M1 cells. Furthermore, STAT3 regulates cell movement, such as leukocyte, epidermal cell, and keratinocyte migration. STAT3 also appears to regulate B cell differentiation into antibody-forming plasma cells. Since the IL-6/gp130/STAT3 signaling pathway is involved in both B cell growth and differentiation into plasma cells it is likely to play a central role in the generation of plasma cell neoplasias. Oncogene (2000).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cell Differentiation*
  • Cell Division
  • Cell Movement
  • Cell Survival
  • Cytokine Receptor gp130
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Interleukin-6 / metabolism*
  • Membrane Glycoproteins / metabolism
  • Plasmacytoma / metabolism
  • Plasmacytoma / pathology
  • Receptors, Interleukin-6 / metabolism*
  • STAT3 Transcription Factor
  • Signal Transduction*
  • Trans-Activators / metabolism*

Substances

  • Antigens, CD
  • DNA-Binding Proteins
  • IL6ST protein, human
  • Interleukin-6
  • Membrane Glycoproteins
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Cytokine Receptor gp130