Fibroblast growth factor receptor 4 (FGFR4) mediates signaling to the prolactin but not the FGFR4 promoter

Am J Physiol Endocrinol Metab. 2002 Sep;283(3):E490-5. doi: 10.1152/ajpendo.00166.2002.

Abstract

Fibroblast growth factor receptors (FGFRs) have been implicated in a multitude of activities. Signaling of the 23 members of the FGF family is mediated through FGFR1-4. We show that FGF-19, which selectively binds FGFR4, can induce prolactin (PRL) but not growth hormone expression. FGF-19 also stimulated MAPK activation, an effect that was abrogated by a soluble dominant negative (dn) form of FGFR4. The response of the pituitary PRL promoter to FGF maps to an Ets-Pit1 binding site. We have previously shown that the hematopoietic zinc finger-containing transcription factor Ikaros (Ik) regulates FGFR4 as part of an overlapping site with that for an Ets-type factor in the FGFR4 promoter. Thus, we examined whether FGF-19 might regulate its own receptor through the Ets-Ik element in the FGFR4 promoter. Ets stimulated and dn-Ets inhibited basal FGFR4 and PRL promoter activity. In contrast, Ets enhanced FGF-19-induced PRL activation but failed to confer an effect for FGF-19 on the FGFR4 promoter. We conclude that FGFR4 mediates FGF-19 signaling to the PRL promoter. Our data also suggest a possible functional role for Ik in sorting Ets signals to the FGFR4 promoter, as distinct from the PRL promoter, where Ets partners with Pit1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / physiology
  • Cell Line
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Prolactin / genetics*
  • Promoter Regions, Genetic / physiology*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-ets
  • Rats
  • Receptor, Fibroblast Growth Factor, Type 4
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / physiology*
  • Signal Transduction / physiology*
  • Transcription Factors / physiology

Substances

  • FGF19 protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Receptors, Fibroblast Growth Factor
  • Transcription Factors
  • Fibroblast Growth Factors
  • Prolactin
  • FGFR4 protein, human
  • Fgfr4 protein, rat
  • Receptor, Fibroblast Growth Factor, Type 4