title: Manipulating signal delivery - plasma-membrane ERK activation in aPKC-dependent migration.
abstract: Members of the PKC superfamily have been implicated in various migratory models and in particular in spatially restricted processes. However, defining the precise local events that underlie the PKC-dependent processes is constrained by the unspecific nature of interventions. Here we address this problem in relation to atypical PKC (aPKC) action, which in conjunction with the exocyst complex controls the polarised delivery of promigratory signals. A drug-dependent recruitment approach was employed to manipulate the local recruitment of signals to the leading edge of migrating cells, under conditions where the aPKC-exocyst control is globally abrogated. We found that activation of ERK but not JNK at focal adhesions recovers the majority of the migratory loss attributed to ERK action, demonstrating a necessary role for active plasma membrane ERK in the downstream signalling of aPKC-dependent migration. The data further show that restored focal adhesion dynamics are a contributing mechanism through which localized ERK activity influences this aPKC-exocyst-dependent migration.
authors.affiliation: Protein Phosphorylation Laboratory, Cancer Research UK, London Research Institute, London, WC2A 3PX, UK.
authors.forename: Katrina
authors.initials: K
authors.lastname: Boeckeler
authors.forename: Carine
authors.initials: C
authors.lastname: Rosse
authors.forename: Michael
authors.initials: M
authors.lastname: Howell
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Parker
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D022001:Focal Adhesions / Q000201:enzymology; D007668:Kidney / Q000166:cytology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C539629:AP 21967; D051419:Paxillin; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D020123:Sirolimus