Min X, Wang S, Zhang X, Sun N, Kim KM

PKC?II, 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 PKC?II with altered phosphorylation and protein interaction behaviors to identify the cellular mechanisms underlying the activation of PKC?II. Our results show that 3-phosphoinositide-dependent protein ...

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kinase-1 (PDK1)-mediated constitutive phosphorylation of PKC?II at the activation loop (T500) is required for phorbol ester-induced nuclear entry and subsequent Mdm2-mediated ubiquitination of PKC?II, whereas ubiquitination of PKC?II is required for the PDK1-mediated inducible phosphorylation of PKC?II at T500 in the nucleus. After moving out of the nucleus, PKC?II interacts with actin, undergoes inducible mTORC2-mediated phosphorylation at the turn motif (T641), interacts with clathrin, and then translocates to the plasma membrane. This overall cascade of cellular events intertwined with the phosphorylation at critical residues and Mdm2-mediated ubiquitination in the nucleus and along with interactions with actin and clathrin plays roles that encompass the core processes of PKC activation.

Date: Apr. 01, 2023

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