Regulation of Peroxisome Proliferator-activated Receptor γ Activity by Mitogen-activated Protein Kinase

• Published in: The Journal of biological chemistry Vol. 272; no. 16; p. 10811
• Main Authors: Heidi S. Camp, Sherrie R. Tafuri
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 18-04-1997
• DOI: 10.1074/jbc.272.16.10811
• EISSN: 1083-351X
• ISSN: 0021-9258

Adipocyte differentiation is regulated both positively and negatively by external growth factors such as insulin, platelet-derived
growth factor (PDGF), and epidermal growth factor (EGF). A key component of the adipocyte differentiation process is PPARγ,
peroxisomal proliferator-activated receptor γ. To determine the relationship between PPARγ activation and growth factor stimulation
in adipogenesis, we investigated the effects of PDGF and EGF on PPARγ1 activity. PDGF treatment decreased ligand-activated
PPARγ1 transcriptional activity in a transient reporter assay. In vivo [ 32 P]orthophosphate labeling experiments demonstrated that PPARγ1 is a phosphoprotein that undergoes EGF-stimulated MEK/mitogen-activated
protein (MAP) kinase-dependent phosphorylation. Purified PPARγ1 protein was phosphorylated in vitro by recombinant activated MAP kinase. Examination of the PPARγ1 sequence revealed a single MAP kinase consensus recognition
site at Ser 82 . Mutation of Ser 82 to Ala inhibited both in vitro and in vivo phosphorylation and growth factor-mediated transcriptional repression. Therefore, phosphorylation of PPARγ1 by MAP kinase
contributes to the reduction of PPARγ1 transcriptional activity by growth factor treatment.