An aPKC-Exocyst Complex Controls Paxillin Phosphorylation and Migration through Localised JNK1 Activation Export

@article{citeulike:6064500, abstract = {Atypical protein kinase C (aPKC) isoforms have been implicated in cell polarisation and migration through association with Cdc42 and Par6. In distinct migratory models, the Exocyst complex has been shown to be involved in secretory events and migration. By RNA interference (RNAi) we show that the polarised delivery of the Exocyst to the leading edge of migrating NRK cells is dependent upon aPKCs. Reciprocally we demonstrate that aPKC localisation at the leading edge is dependent upon the Exocyst. The basis of this inter-dependence derives from two-hybrid, mass spectrometry, and co-immunoprecipitation studies, which demonstrate the existence of an aPKC\^{a}€ ” Exocyst interaction mediated by Kibra. Using RNAi and small molecule inhibitors, the aPKCs, Kibra, and the Exocyst are shown to be required for NRK cell migration and it is further demonstrated that they are necessary for the localized activation of JNK at the leading edge. The migration associated control of JNK by aPKCs determines JNK phosphorylation of the plasma membrane substrate Paxillin, but not the phosphorylation of the nuclear JNK substrate, c-jun. This plasma membrane localized JNK cascade serves to control the stability of focal adhesion complexes, regulating migration. The study integrates the polarising behaviour of aPKCs with the pro-migratory properties of the Exocyst complex, defining a higher order complex associated with the localised activation of JNK at the leading edge of migrating cells that determines migration rate.}, author = {Rosse, Carine and Formstecher, Etienne and Boeckeler, Katrina and Zhao, Yingming and Kremerskothen, Joachim and White, Michael D. and Camonis, Jacques H. and Parker, Peter J.}, citeulike-article-id = {6064500}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pbio.1000235}, day = {3}, doi = {10.1371/journal.pbio.1000235}, journal = {PLoS Biol}, keywords = {maximum-likelifood, molecular\_dynamics, programming, protein-structure}, month = {November}, number = {11}, pages = {e1000235+}, posted-at = {2009-11-06 09:15:04}, priority = {2}, publisher = {Public Library of Science}, title = {An aPKC-Exocyst Complex Controls Paxillin Phosphorylation and Migration through Localised JNK1 Activation}, url = {http://dx.doi.org/10.1371/journal.pbio.1000235}, volume = {7}, year = {2009} }

TY - JOUR ID - citeulike:6064500 L3 - citeulike-article-id:6064500 N2 - Atypical protein kinase C (aPKC) isoforms have been implicated in cell polarisation and migration through association with Cdc42 and Par6. In distinct migratory models, the Exocyst complex has been shown to be involved in secretory events and migration. By RNA interference (RNAi) we show that the polarised delivery of the Exocyst to the leading edge of migrating NRK cells is dependent upon aPKCs. Reciprocally we demonstrate that aPKC localisation at the leading edge is dependent upon the Exocyst. The basis of this inter-dependence derives from two-hybrid, mass spectrometry, and co-immunoprecipitation studies, which demonstrate the existence of an aPKC–Exocyst interaction mediated by Kibra. Using RNAi and small molecule inhibitors, the aPKCs, Kibra, and the Exocyst are shown to be required for NRK cell migration and it is further demonstrated that they are necessary for the localized activation of JNK at the leading edge. The migration associated control of JNK by aPKCs determines JNK phosphorylation of the plasma membrane substrate Paxillin, but not the phosphorylation of the nuclear JNK substrate, c-jun. This plasma membrane localized JNK cascade serves to control the stability of focal adhesion complexes, regulating migration. The study integrates the polarising behaviour of aPKCs with the pro-migratory properties of the Exocyst complex, defining a higher order complex associated with the localised activation of JNK at the leading edge of migrating cells that determines migration rate. IS - 11 JF - PLoS Biol TI - An aPKC-Exocyst Complex Controls Paxillin Phosphorylation and Migration through Localised JNK1 Activation PB - Public Library of Science VL - 7 SP - e1000235 KW - maximum-likelifood KW - molecular_dynamics KW - programming KW - protein-structure AU - Rosse, Carine AU - Formstecher, Etienne AU - Boeckeler, Katrina AU - Zhao, Yingming AU - Kremerskothen, Joachim AU - White, Michael AU - Camonis, Jacques AU - Parker, Peter PY - 2009/11/03/ UR - http://dx.doi.org/10.1371/journal.pbio.1000235 ER -