beta-Neuregulin and autocrine mediated survival of Schwann cells requires activity of Ets family transcription factors

Mol Cell Neurosci. 2002 May;20(1):154-67. doi: 10.1006/mcne.2002.1109.

Abstract

Members of the Ets transcription factor family function in many biological processes. We show the presence of Ets transcription factors, most prominently Net, in neonatal rat Schwann cells, and demonstrate Ets-dependent transcription under conditions where the cells are exposed to autocrine signals or autocrine signals plus beta-neuregulin. Using the potent MAPK kinase inhibitor U0126 we also confirm that the MAP kinase pathway, an activator of Ets transcription, is involved in beta-neuregulin mediated Schwann cell survival. Furthermore, we find that expression of dominant negative Ets1 (N70-Ets1) inhibits both the beta-neuregulin and autocrine survival of Schwann cells. In contrast, the survival of Schwann cells mediated by lysophosphatidic acid (LPA) is unaffected by expression of a dominant negative Ets molecule. These data demonstrate that distinct autocrine and beta-neuregulin survival signals converge in their requirement for Ets dependent transcription in Schwann cell survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Autocrine Communication / drug effects
  • Autocrine Communication / physiology*
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Survival / drug effects
  • Cell Survival / physiology*
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins*
  • Enzyme Inhibitors / pharmacology
  • GA-Binding Protein Transcription Factor
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Lysophospholipids / metabolism
  • Lysophospholipids / pharmacology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology
  • Neuregulin-1 / metabolism*
  • Peripheral Nerves / cytology
  • Peripheral Nerves / growth & development*
  • Peripheral Nerves / metabolism*
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-ets
  • Rats
  • Rats, Sprague-Dawley
  • Repressor Proteins / metabolism
  • Schwann Cells / cytology
  • Schwann Cells / drug effects
  • Schwann Cells / metabolism*
  • Sciatic Nerve / cytology
  • Sciatic Nerve / growth & development
  • Sciatic Nerve / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription Factors / metabolism*
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Enzyme Inhibitors
  • Ets1 protein, rat
  • GA-Binding Protein Transcription Factor
  • Lysophospholipids
  • Neuregulin-1
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins
  • Transcription Factors
  • net protein, Drosophila
  • neuregulin beta