Protein Ser/Thr phosphatase-6 is required for maintenance of E-cadherin at adherens junctions.
BMC Cell Biol
; 14: 42, 2013 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-24063632
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Caderinas
/
Fosfoproteínas Fosfatases
/
Junções Aderentes
/
Caseína Quinase I
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article