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PKCβII inhibits the ubiquitination of β‐arrestin2 in an autophosphorylation‐dependent manner
Author(s) -
Zheng Mei,
Zhang Xiaohan,
Guo Shuohan,
Zhang Xiaowei,
Choi Hyun Jin,
Lee Moo-Yeol,
Kim Kyeong-Man
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.10.031
Subject(s) - autophosphorylation , g protein coupled receptor , microbiology and biotechnology , protein kinase c , internalization , arrestin , g protein coupled receptor kinase , chemistry , beta adrenergic receptor kinase , protein kinase a , phosphorylation , biology , biochemistry , receptor , signal transduction
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 D 2 receptor and β 2 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.