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J Cell Biol. 2008 May 19;181(4):605-13. doi: 10.1083/jcb.200712133. Epub 2008 May 12.

Plakophilin 2: a critical scaffold for PKC alpha that regulates intercellular junction assembly.

Author information

1
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

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.

PMID:
18474624
PMCID:
PMC2386101
DOI:
10.1083/jcb.200712133
[Indexed for MEDLINE]
Free PMC Article

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