西亚试剂：Regulation of PKC Inactivation by FADD

Regulation of PKC Inactivation by FADD

Wei Cheng, Lu Wang, Rong Zhang, Pan Du, Bingya Yang, Hongqin Zhuang, Bo Tang, Chun Yao, Mei Yu, Yuxuan Wang, Jing Zhang, Wu Yin, Jiahuang Li, Weijuan Zheng, Min Lu and Zichun Hua.

TProtein kinase C (PKC) plays important roles in diverse cellular processes. PKC has been implicated in regulating FADD, an important adaptor protein involved in regulating death receptor mediated apoptosis.FADD also plays an important role in non-apoptosis processes.
The functional interaction of PKC and FADD in non-apoptotic processes has not been examined. In this study, we show that FADD is involved in maintaining the phosphorylation of turn motif (TM) and hydrophobic motif (HM) in the activated conventional PKC (cPKC).
A phosphoryl-mimicking mutation (S191D) in FADD (FADD-D) abolished the function of FADD in the facilitation of the TM and HM dephosphorylation of cPKC, suggesting that phosphorylation of S191 negatively regulates FADD.We show that FADD interacts with PP2A, a major phosphatase involved in dephosphorylation of activated cPKC and FADD deficiency abolished PP2A mediated dephosphorylation of cPKC. We show that FADD deficiency leads increased stability and activity of cPKC which in turn promotes cytoskeleton reorganization, cell motility and chemotaxis.Collectively, these results reveal a novel function of FADD in a non-apoptotic process by modulating cPKC dephosphorylation, stability and signaling termination.