RT Journal Article SR Electronic T1 Activation of Mitogen-Activated Protein Kinases by Peroxisome Proliferator-Activated Receptor Ligands: An Example of Nongenomic Signaling JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 933 OP 941 DO 10.1124/mol.105.012260 VO 68 IS 4 A1 Gardner, Olivia S. A1 Dewar, Brian J. A1 Graves, Lee M. YR 2005 UL http://molpharm.aspetjournals.org/content/68/4/933.abstract AB 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.