Activation of mitogen-activated protein kinases by peroxisome proliferator-activated receptor ligands: an example of nongenomic signaling.
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.
Gardner
Olivia S
OS
Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599, USA.
Dewar
Brian J
BJ
Graves
Lee M
LM
D000818:Animals; D004789:Enzyme Activation; D016678:Genome; D006801:Humans; D008024:Ligands; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D015398:Signal Transduction
D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D020928:Mitogen-Activated Protein Kinases