| First Author | Hinds TD Jr | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 50 | Pages | 42911-22 |
| PubMed ID | 21994940 | Mgi Jnum | J:178732 |
| Mgi Id | MGI:5299993 | Doi | 10.1074/jbc.M111.311662 |
| Citation | Hinds TD Jr, et al. (2011) Protein Phosphatase 5 Mediates Lipid Metabolism through Reciprocal Control of Glucocorticoid Receptor and Peroxisome Proliferator-activated Receptor-gamma (PPARgamma). J Biol Chem 286(50):42911-22 |
| abstractText | Glucocorticoid receptor-alpha (GRalpha) and peroxisome proliferator-activated receptor-gamma (PPARgamma) regulate adipogenesis by controlling the balance between lipolysis and lipogenesis. Here, we show that protein phosphatase 5 (PP5), a nuclear receptor co-chaperone, reciprocally modulates the lipometabolic activities of GRalpha and PPARgamma. Wild-type and PP5-deficient (KO) mouse embryonic fibroblast cells were used to show binding of PP5 to both GRalpha and PPARgamma. In response to adipogenic stimuli, PP5-KO mouse embryonic fibroblast cells showed almost no lipid accumulation with reduced expression of adipogenic markers (aP2, CD36, and perilipin) and low fatty-acid synthase enzymatic activity. This was completely reversed following reintroduction of PP5. Loss of PP5 increased phosphorylation of GRalpha at serines 212 and 234 and elevated dexamethasone-induced activity at prolipolytic genes. In contrast, PPARgamma in PP5-KO cells was hyperphosphorylated at serine 112 but had reduced rosiglitazone-induced activity at lipogenic genes. Expression of the S112A mutant rescued PPARgamma transcriptional activity and lipid accumulation in PP5-KO cells pointing to Ser-112 as an important residue of PP5 action. This work identifies PP5 as a fulcrum point in nuclear receptor control of the lipolysis/lipogenesis equilibrium and as a potential target in the treatment of obesity. |
