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BMC Cell Biol. 2013 Sep 25;14:42. doi: 10.1186/1471-2121-14-42.

Protein Ser/Thr phosphatase-6 is required for maintenance of E-cadherin at adherens junctions.

Author information

1
Center for Cell Signaling and Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Box 800577, West Complex MSB 7225, Charlottesville, Virginia 22908, USA. db8g@virginia.edu.

Abstract

BACKGROUND:

Epithelial 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.

RESULTS:

This 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.

CONCLUSIONS:

PP6c 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.

PMID:
24063632
PMCID:
PMC3856536
DOI:
10.1186/1471-2121-14-42
[Indexed for MEDLINE]
Free PMC Article

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