Phosphorylation of PPARs: from molecular characterization to physiological relevance.
In addition to their ligand-mediated activation, nuclear receptor activity is finely tuned by their phosphorylation status. PPARs are phosphorylated by several kinases (PKA, PKC, MAPKs, and AMPK), which affect their activity in a ligand-dependent or -independent manner according to the isoform and cellular context. Molecular consequences are multiple, including changes in ligand affinity, DNA binding, recruitment of transcriptional cofactors, proteasome degradation... Finally, the physiological relevance of PPAR phosphorylation is discussed.
Diradourian
Claire
C
Département d'Endocrinologie, Institut Cochin, Inserm U567 CNRS UMR8104, Université Paris V, 24, rue du Faubourg Saint Jacques 75014 Paris, France.
Girard
Jean
J
Pégorier
Jean-Paul
JP
D055372:AMP-Activated Protein Kinases; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D047494:PPAR delta / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D009097:Multienzyme Complexes; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases