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Glycogen Synthase Kinase 3 phosphorylates and affects the stability of Peroxisome proliferator‐activated receptor α
Author(s) -
Burns Katherine Anne,
Heuvel Jack Vanden
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1020-c
Subject(s) - gsk 3 , phosphorylation , peroxisome proliferator activated receptor , gsk3b , glycogen synthase , protein kinase a , biochemistry , biology , microbiology and biotechnology , chemistry , receptor
PPARα (peroxisome‐proliferator‐activated receptor α) is a member of the nuclear hormone receptor family of transcription factors that is ivolved in the control of fatty acid catabolism. Much interest has focused on the regulation of PPARα activity by phosphorylation. Phosphorylation of PPARα by MAPK, PKA and PKC has been shown to regulate its activity; however, it is likely that other kinases are involved in PPARα regulation. Of the predicted phosphorylation sites within PPARα, five are conserved GSK3 (glycogen synthase kinase 3) sites. GSK3 is a proline directed serine/theronine‐specific kinase that phosphorylates at SXXXS sites and is involved in cell cycle regulation and insulin signaling. In the present study, the role of GSK3β in PPARα signaling was assessed. Our data show that GSK3 phosphorylates PPARα at serine 73 in the A/B domain (AF‐1). The phosphorylation of PPARα by GSK3 decreases the stability of PPARα by increasing its turnover which is mediated by the ubiquitin proteasome system. These findings suggest PPARα and GSK3, two proteins important in cell cycle regulation, fatty acid oxidation, obesity and diabetes, are directly and functionally connected.