title: Plakophilin 2: a critical scaffold for PKC alpha that regulates intercellular junction assembly.
abstract: Plakophilins (PKPs) are armadillo family members related to the classical cadherin-associated protein p120(ctn). PKPs localize to the cytoplasmic plaque of intercellular junctions and participate in linking the intermediate filament (IF)-binding protein desmoplakin (DP) to desmosomal cadherins. In response to cell-cell contact, PKP2 associates with DP in plaque precursors that form in the cytoplasm and translocate to nascent desmosomes. Here, we provide evidence that PKP2 governs DP assembly dynamics by scaffolding a DP-PKP2-protein kinase C alpha (PKC alpha) complex, which is disrupted by PKP2 knockdown. The behavior of a phosphorylation-deficient DP mutant that associates more tightly with IF is mimicked by PKP2 and PKC alpha knockdown and PKC pharmacological inhibition, all of which impair junction assembly. PKP2 knockdown is accompanied by increased phosphorylation of PKC substrates, raising the possibility that global alterations in PKC signaling may contribute to pathogenesis of congenital defects caused by PKP2 deficiency.
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Bass-Zubek
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Hobbs
authors.forename: Evangeline V
authors.initials: EV
authors.lastname: Amargo
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Garcia
authors.forename: Sherry N
authors.initials: SN
authors.lastname: Hsieh
authors.forename: Xinyu
authors.initials: X
authors.lastname: Chen
authors.forename: James K
authors.initials: JK
authors.lastname: Wahl
authors.forename: Mitchell F
authors.initials: MF
authors.lastname: Denning
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Green
mesh_terms: D002460:Cell Line; D051180:Desmoplakins / Q000378:metabolism; D003896:Desmosomes / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D051191:Plakophilins / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D051180:Desmoplakins; D051191:Plakophilins; D012694:Serine; D051571:Protein Kinase C-alpha; D013755:Tetradecanoylphorbol Acetate