Leukemia inhibitory factor and ciliary neurotrophic factor increase activated Ras in a neuroblastoma cell line and in sympathetic neuron cultures

Michael A. Schwarzschild, William T. Dauer, Susan E. Lewis, Lila K. Hamill, J. Stephen Fink, Steven E. Hyman

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The cytokines leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) have been implicated in determination of neuronal phenotype as well as promotion of neuronal survival. However, the intracellular mechanisms by which their signals are transduced remain poorly understood. We have previously studied the regulation of vasoactive intestinal polypeptide gene expression by LIF and CNTF in the NBFL neuroblastoma cell line. Because these cytokines induce tyrosine phosphorylation that may lead to Ras activation, we explored a possible role for Ras in LIF- and CNTF-induced signal transduction. In NBFL cells LIF increases activated Ras in a rapid, transient, and concentration-dependent manner. CNTF and a related cytokine, oncostatin M, produce similar increases. CNTF and LIF also increase activated Ras in neuron-enriched dissociated cultures of sympathetic ganglia. Moreover, these cytokines rapidly and transiently induce specific tyrosine- phosphorylated proteins, p165 and p195. The protein kinase inhibitors K252a and staurosporine block LIF-induced increases in tyrosine phosphorylation, activated Ras, and vasoactive intestinal polypeptide mRNA in NBFL cells. These data support a possible role for Ras in the cell differentiation effects of LIF and CNTF.

Original languageEnglish (US)
Pages (from-to)1246-1254
Number of pages9
JournalJournal of Neurochemistry
Volume63
Issue number4
StatePublished - Oct 1 1994
Externally publishedYes

Keywords

  • Ciliary neurotrophic factor
  • Leukemia inhibitory factor
  • Neuroblastoma
  • Oncostatin M
  • Ras
  • Sympathetic neurons
  • Tyrosine phosphorylation
  • gp130

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Leukemia inhibitory factor and ciliary neurotrophic factor increase activated Ras in a neuroblastoma cell line and in sympathetic neuron cultures'. Together they form a unique fingerprint.

  • Cite this