PKCβII activation requires nuclear trafficking for phosphorylation and Mdm2-mediated ubiquitination.

ABSTRACT: PKCβII, a conventional PKC family member, plays critical roles in the regulation of a variety of cellular functions. Here, we employed loss-of-function approaches and mutants of PKCβII with altered phosphorylation and protein interaction behaviors to identify the cellular mechanisms underlying the activation of PKCβII. Our results show that 3-phosphoinositide-dependent protein kinase-1 (PDK1)-mediated constitutive phosphorylation of PKCβII at the activation loop (T500) is required for phorbol ester-induced nuclear entry and subsequent Mdm2-mediated ubiquitination of PKCβII, whereas ubiquitination of PKCβII is required for the PDK1-mediated inducible phosphorylation of PKCβII at T500 in the nucleus. After moving out of the nucleus, PKCβII interacts with actin, undergoes inducible mTORC2-med

SUBMITTER: Min X 

PROVIDER: S-EPMC9887771 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature