Characterization of a pathway for ciliary neurotrophic factor signaling to the nucleus

Science. 1993 Dec 3;262(5139):1575-9. doi: 10.1126/science.7504325.

Abstract

Components of a signaling pathway that couples the ciliary neurotrophic factor (CNTF) receptor to induction of transcription were identified. CNTF stimulated the tyrosine phosphorylation of p91, a protein implicated in interferon signaling pathways, and of two proteins that are distinct but related to p91. Tyrosine-phosphorylated p91 translocated to the nucleus, where p91 and p91-related proteins bound to a DNA sequence found in promoters of genes responsive to CNTF. This DNA sequence, when inserted upstream of a reporter gene, conferred a transcriptional response to CNTF. A pathway that transduces interferon signals may therefore have a more general function in the propagation of responses to certain neurotrophic factors.

Publication types

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

MeSH terms

  • Base Sequence
  • Biological Transport / physiology
  • Cell Nucleus / metabolism*
  • Ciliary Neurotrophic Factor
  • DNA-Binding Proteins / biosynthesis
  • Fibroblast Growth Factor 2 / physiology
  • Gene Expression Regulation / physiology
  • HeLa Cells
  • Humans
  • Interferon-alpha / physiology
  • Interferon-gamma / physiology
  • Molecular Sequence Data
  • Molecular Weight
  • Nerve Tissue Proteins / physiology*
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / chemistry
  • Phosphotyrosine
  • Regulatory Sequences, Nucleic Acid / physiology
  • Signal Transduction / physiology*
  • Transcription, Genetic / physiology*
  • Tumor Cells, Cultured
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis

Substances

  • Ciliary Neurotrophic Factor
  • DNA-Binding Proteins
  • Interferon-alpha
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Fibroblast Growth Factor 2
  • Phosphotyrosine
  • Tyrosine
  • Interferon-gamma