title: Trophinin-mediated cell adhesion induces apoptosis of human endometrial epithelial cells through PKC-δ.
abstract: Trophinin is an intrinsic membrane protein expressed in trophectoderm cells of embryos and in uterine epithelial cells. Trophinin potentially mediates apical cell adhesion at human embryo implantation sites through trophinin-trophinin binding in these two cell types. Trophinin-mediated cell adhesion activates trophectoderm cells for invasion, whereas the effect of adhesion on maternal side is not known. We show that addition of GWRQ peptide, a previously established peptide that mimics trophinin-mediated cell adhesion, to human endometrial epithelial cells expressing trophinin induces their apoptosis. FAS involvement was excluded, as GWRQ did not bind to FAS, and FAS knockdown did not alter GWRQ-induced apoptosis. Immunoblotting analyses of protein kinases revealed an elevation of PKC-d protein in GWRQ-bound endometrial epithelial cells. In the absence of GWRQ, PKC-d associated with trophinin and remained cytoplasmic, but after GWRQ binding to the trophinin extracellular domain, PKC-d became tyrosine phosphorylated, dissociated from trophinin, and entered the nucleus. In PKC-d knockdown endometrial cells, GWRQ did not induce apoptosis.
authors.affiliation: Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Tamura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugihara
authors.forename: Tomoya O
authors.initials: TO
authors.lastname: Akama
authors.forename: Michiko N
authors.initials: MN
authors.lastname: Fukuda
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology / Q000201:enzymology*; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D005260:Female; D006801:Humans; D051745:Protein Kinase C-delta / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; C093649:TRO protein, human; D051745:Protein Kinase C-delta