Activation of mitogen-activated protein kinases by peroxisome proliferator-activated receptor ligands: an example of nongenomic signaling

Mol Pharmacol. 2005 Oct;68(4):933-41. doi: 10.1124/mol.105.012260. Epub 2005 Jul 14.

Abstract

Peroxisome proliferator-activated receptors (PPARs) are a subfamily of nuclear hormone receptors that function as ligand-activated transcription factors to regulate lipid metabolism and homeostasis. In addition to their ability to promote gene transcription in a PPAR-dependent manner, ligands for this receptor family have recently been shown to induce mitogen-activated protein kinase (MAPK) phosphorylation. It is noteworthy that the transcriptional changes induced by PPAR ligands can be separated into distinct PPAR- and MAPK-dependent signaling pathways, suggesting that MAPKs alone mediate some of the effects of PPAR agonists in a nongenomic manner. This review will highlight recent studies that elucidate the nongenomic mechanisms of PPAR ligand-induced MAPK phosphorylation. The potential relevance of MAPK signaling in PPAR biology is also discussed.

Publication types

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

MeSH terms

  • Animals
  • Enzyme Activation
  • Genome
  • Humans
  • Ligands
  • Mitogen-Activated Protein Kinases / metabolism*
  • Peroxisome Proliferator-Activated Receptors / metabolism*
  • Signal Transduction*

Substances

  • Ligands
  • Peroxisome Proliferator-Activated Receptors
  • Mitogen-Activated Protein Kinases