Protein Ser-Thr phosphatase-6 is required for maintenance of E-cadherin at adherens junctionsReport as inadecuate

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BMC Cell Biology

, 14:42

Cell-cell contacts and adhesion


BackgroundEpithelial tissues depend on intercellular homodimerization of E-cadherin and loss of E-cadherin is central to the epithelial to mesenchymal transition seen in multiple human diseases. Signaling pathways regulate E-cadherin function and cellular distribution via phosphorylation of the cytoplasmic region by kinases such as casein kinases but the protein phosphatases involved have not been identified.

ResultsThis study shows protein Ser-Thr phosphatase-6 catalytic subunit PP6c is expressed in epithelial tissue and its mRNA and protein are robustly up-regulated in epithelial cell lines at high vs. low density. PP6c accumulates at adherens junctions, not tight junctions, co-immunoprecipitates with E-cadherin-catenin complexes without a canonical SAPS subunit, and associates directly with the E-cadherin cytoplasmic tail. Inducible shRNA knockdown of PP6c dispersed E-cadherin from the cell surface and this response was reversed by chemical inhibition of casein kinase-1 and prevented by alanine substitution of Ser846 in murine E-cadherin.

ConclusionsPP6c associates with E-cadherin in adherens junctions and is required to oppose casein kinase-1 to maintain cell surface localization of E-cadherin. There is feedback signaling to enhance PP6c transcription and boost protein levels in high density epithelial cells.

KeywordsCatenin Casein kinase SAPS Occludin Caco-2 ARPE-19 AbbreviationsPP6Protein phosphatase-6

PP6cProtein phosphatase-6 catalytic subunit

CK2Casein kinase-2

CK1Casein kinase-1

GSK3Glycogen synthase kinase-3

SDS-PAGESodium dodecyl sulfate polyacrylamide gel electrophoresis.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2121-14-42 contains supplementary material, which is available to authorized users.

Takashi Ohama, Lifu Wang contributed equally to this work.

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Author: Takashi Ohama - Lifu Wang - Erin M Griner - David L Brautigan


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