| http://purl.uniprot.org/citations/12376527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12376527 | http://www.w3.org/2000/01/rdf-schema#comment | "Nectin-1 is a member of the immunoglobulin superfamily and a Ca(2+)-independent adherens junction protein involved in synapse formation. Here we show that nectin-1alpha undergoes intramembrane proteolytic processing analogous to that of the Alzheimer's disease amyloid precursor protein, mediated by a presenilin (PS)-dependent gamma-secretase-like activity. 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment of Chinese hamster ovary cells activated a first proteolytic event, resulting in ectodomain shedding of nectin-1alpha. Subsequent cleavage of the remaining 26-kDa membrane-anchored C-terminal fragment (CTF) was inhibited independently by three specific gamma-secretase inhibitors and by expression of the dominant negative form of PS1. The PS/gamma-secretase-like cleavage product was detected in vivo following proteasome inhibitor treatment of cells. An in vitro gamma-secretase assay confirmed the generation of a 24-kDa nectin-1alpha intracellular domain, peripherally associated with the membrane fraction. We also found nectin-1alpha to interact with the N-terminal fragment of PS1. Finally, gamma-secretase inhibition resulted in beta-catenin release from cell junctions, concomitantly with the accumulation of the 26-kDa nectin-1alpha CTF, suggesting that high levels of nectin-1alpha CTF interfere with TPA-induced remodeling of cell-cell junctions. Our results are consistent with a previously reported role for PS/gamma-secretase in adherens junction function involving cleavage of cadherins. Similar to nectin-1, other members of the immunoglobulin superfamily involved in synapse formation may also serve as substrates for PS/gamma-secretase-like intramembrane proteolytic activity."xsd:string |
| http://purl.uniprot.org/citations/12376527 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m210179200"xsd:string |
| http://purl.uniprot.org/citations/12376527 | http://purl.uniprot.org/core/author | "Kim D.Y."xsd:string |
| http://purl.uniprot.org/citations/12376527 | http://purl.uniprot.org/core/author | "Kovacs D.M."xsd:string |
| http://purl.uniprot.org/citations/12376527 | http://purl.uniprot.org/core/author | "Ingano L.A."xsd:string |
| http://purl.uniprot.org/citations/12376527 | http://purl.uniprot.org/core/date | "2002"xsd:gYear |
| http://purl.uniprot.org/citations/12376527 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/12376527 | http://purl.uniprot.org/core/pages | "49976-49981"xsd:string |
| http://purl.uniprot.org/citations/12376527 | http://purl.uniprot.org/core/title | "Nectin-1alpha, an immunoglobulin-like receptor involved in the formation of synapses, is a substrate for presenilin/gamma-secretase-like cleavage."xsd:string |
| http://purl.uniprot.org/citations/12376527 | http://purl.uniprot.org/core/volume | "277"xsd:string |
| http://purl.uniprot.org/citations/12376527 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12376527 |
| http://purl.uniprot.org/citations/12376527 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/12376527 |
| http://purl.uniprot.org/uniprot/#_Q9JKF6-mappedCitation-12376527 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/12376527 |
| http://purl.uniprot.org/uniprot/Q9JKF6 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/12376527 |