PKCβII inhibits the ubiquitination of β-arrestin2 in an autophosphorylation-dependent manner

Mei Zheng, Xiaohan Zhang, Shuohan Guo, Xiaowei Zhang, Hyun Jin Choi, Moo Yeol Lee, Kyeong Man Kim

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

GPCR kinase 2 (GRK2)/β-arrestins and protein kinase A (PKA)/protein kinase C (PKC) mediate homologous and heterologous regulations of GPCRs, respectively. Conventional protein kinase C enzymes (PKCs), as exemplified by PKCβII, selectively inhibit internalization of dopamine D2 receptor and β2 adrenoceptor in a β-arrestin- but not GRK2-dependent manner. PKCβII interacts with β-arrestin2 upon autophosphorylation at T250, and inhibits the receptor internalization by decreasing the ubiquitination of β-arrestin2. PKCβII interferes with the interaction between β-arrestin2 and MDM2 in the cytosol, resulting in the redistribution of MDM2 to the nucleus. Subsequently, deubiquitination of β-arrestin2 and inhibition of agonist-induced receptor internalization follow. Thus, our study suggests that the extent of β-arrestin ubiquitination and the autophosphorylation status of PKCs determine PKCβII-mediated inhibition of homologous regulatory processes of GPCRs. A novel regulatory mechanism for the endocytosis of GPCRs is proposed. Conventional PKCs, exemplified as PKCβII, inhibit the internalization of GPCRs. PKCβII inhibits the ubiquitination of β-arrestin2 in an autophosphorylation-dependent manner. Interaction between MDM2 and β-arrestin2 is inhibited by PKCβII in the cytosol, and MDM2 is redistributed to the nucleus.

Original languageEnglish
Pages (from-to)3929-3937
Number of pages9
JournalFEBS Letters
Volume589
Issue number24
DOIs
StatePublished - 21 Dec 2015

Keywords

  • Autophosphorylation
  • Conventional PKC
  • G protein-coupled receptor
  • GPCR kinase 2
  • Ubiquitination
  • β-Arrestin

Fingerprint

Dive into the research topics of 'PKCβII inhibits the ubiquitination of β-arrestin2 in an autophosphorylation-dependent manner'. Together they form a unique fingerprint.

Cite this