Ligand-independent orphan receptor TR2 activation by phosphorylation at the DNA-binding domain

Shaukat Ali Khan, Sung Wook Park, M. D.Mostaqul Huq, Li-Na Wei

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)123-130
Number of pages8
JournalProteomics
Volume6
Issue number1
DOIs
StatePublished - Jan 2006

Keywords

  • Interaction
  • Orphan receptor
  • Phosphorylation
  • p300/CBP-associated factor

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