Plakophilin 2: A critical scaffold for PKCα that regulates intercellular junction assembly

Amanda E. Bass-Zubek, Ryan P. Hobbs, Evangeline V. Amargo, Nicholas J. Garcia, Sherry N. Hsieh, Xinyu Chen, James K. Wahl, Mitchell F. Denning, Kathleen J. Green

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Plakophilins (PKPs) are armadillo family members related to the classical cadherin-associated protein p120ctn. 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 Cα (PKCα) 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 PKCα 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.

Original languageEnglish (US)
Pages (from-to)605-613
Number of pages9
JournalJournal of Cell Biology
Volume181
Issue number4
DOIs
StatePublished - May 19 2008

ASJC Scopus subject areas

  • Cell Biology

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    Bass-Zubek, A. E., Hobbs, R. P., Amargo, E. V., Garcia, N. J., Hsieh, S. N., Chen, X., Wahl, J. K., Denning, M. F., & Green, K. J. (2008). Plakophilin 2: A critical scaffold for PKCα that regulates intercellular junction assembly. Journal of Cell Biology, 181(4), 605-613. https://doi.org/10.1083/jcb.200712133