| http://purl.uniprot.org/citations/24752297 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24752297 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24752297 | http://www.w3.org/2000/01/rdf-schema#comment | "Lrrc8a is a ubiquitously expressed gene that encodes a leucine-rich repeat (LRR)-containing protein detected at higher levels on the surface of thymocytes than on other immune cells. We generated Lrrc8a(-/-) mice to investigate the role of LRRC8A in lymphocyte development and function. Lrrc8a(-/-) mice had increased prenatal and postnatal mortality, growth retardation, and multiple tissue abnormalities. Lrrc8a(-/-) mice displayed a modest block in B cell development but intact intrinsic B cell function. In contrast, both Lrrc8a(-/-) mice and Lrrc8a(-/-)→Rag2(-/-) bone marrow chimeras exhibited a severe cell-intrinsic block in early thymic development, with decreased proliferation and increased apoptosis of thymocytes, and impaired peripheral T cell function. Thymic epithelial cells expressed an LRRC8A ligand that was critical for double-negative to double-positive thymocyte differentiation and survival in vitro. LRRC8A constitutively associated with the GRB2-GAB2 complex and lymphocyte-specific protein tyrosine kinase (LCK) in thymocytes. LRRC8A ligation activated AKT via the LCK-ZAP-70-GAB2-PI3K pathway, and AKT phosphorylation was markedly reduced in the thymus of Lrrc8a(-/-) mice. These findings reveal an essential role for LRRC8A in T cell development, survival, and function."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.org/dc/terms/identifier | "doi:10.1084/jem.20131379"xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.org/dc/terms/identifier | "doi:10.1084/jem.20131379"xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Park S.Y."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Park S.Y."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Chou J."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Chou J."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Kumar L."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Kumar L."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Geha R.S."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Geha R.S."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "von Andrian U.H."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "von Andrian U.H."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Manis J.P."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Manis J.P."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Poliani P.L."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Poliani P.L."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Borzutzky A."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Borzutzky A."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Hollander G."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Hollander G."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Vollmann E.H."xsd:string |
| http://purl.uniprot.org/citations/24752297 | http://purl.uniprot.org/core/author | "Vollmann E.H."xsd:string |