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Ligand‐independent orphan receptor TR2 activation by phosphorylation at the DNA‐binding domain
Author(s) -
Khan Shaukat Ali,
Park Sung Wook,
Huq M. D. Mostaqul,
Wei LiNa
Publication year - 2006
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200500068
Subject(s) - coactivator , dna binding domain , phosphorylation , orphan receptor , binding domain , ligand (biochemistry) , dna , microbiology and biotechnology , receptor , protein kinase c , chemistry , nuclear receptor , biology , binding site , biochemistry , gene , transcription factor
In a previous report we demonstrated protein kinase C (PKC)‐mediated phosphorylation of the ligand‐binding domain (LBD) of orphan nuclear receptor TR2. In this report, we provide the evidence of PKC‐mediated phosphorylation of the DNA‐binding domain (DBD) of TR2. Two PKC target sites were predicted within the DBD, at Ser‐170 and Ser‐185, but only Ser‐185 was confirmed by MS. Phosphorylation of DBD facilitated DNA binding of the TR2 receptor and its recruiting of coactivator p300/CBP‐associated factor (P/CAF). Ser‐185 was required for DNA binding, whereas both Ser‐170 and Ser‐185 were necessary for receptor interaction with P/CAF. The P/CAF‐interacting domain of TR2 was located in its DBD. A double mutant (Ser‐170 and Ser‐185) of TR2 significantly lowered the activation of its target gene RARβ2 . This study provides the first evidence for ligand‐independent activation of TR2 orphan receptor through PTM at the DBD, which enhanced its DNA‐binding ability and interaction with coactivator P/CAF.