A Cancer-Associated Mutation in Atypical Protein Kinase Cι Occurs in a Substrate-Specific Recruitment Motif

摘要: Atypical protein kinase Cι (PKCι) has roles in cell growth, cellular polarity, and migration, its abundance is frequently increased cancer. We identified a interaction surface containing dibasic motif (RIPR) that bound distinct subset of PKCι substrates including lethal giant larvae 2 (LLGL2) myosin X, but not other such as Par3. Further characterization demonstrated Arg471 this was important for binding to LLGL2, whereas Arg474 critical with indicating multiple complexes could be formed through motif. A somatic mutation the (R471C) most frequent human cancer, intact required normal polarized epithelial morphogenesis three-dimensional cysts. Thus, R471C substitution change-of-function acting at substrate-specific recruitment site selectively disrupt polarizing activity PKCι.