http://purl.uniprot.org/citations/18550856 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/18550856 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/18550856 | http://www.w3.org/2000/01/rdf-schema#comment | "Leukocyte integrins of the beta2 family are essential for immune cell-cell adhesion. In activated cells, beta2 integrins are phosphorylated on the cytoplasmic Thr758, leading to 14-3-3 protein recruitment to the beta2 integrin. The mutation of this phosphorylation site impairs cell adhesion, actin reorganization, and cell spreading. Thr758 is contained in a Thr triplet of beta2 that also mediates binding to filamin. Here, we investigated the binding of filamin, talin, and 14-3-3 proteins to phosphorylated and unphosphorylated beta2 integrins by biochemical methods and x-ray crystallography. 14-3-3 proteins bound only to the phosphorylated integrin cytoplasmic peptide, with a high affinity (K(d), 261 nM), whereas filamin bound only the unphosphorylated integrin cytoplasmic peptide (K(d), 0.5 mM). Phosphorylation did not regulate talin binding to beta2 directly, but 14-3-3 was able to outcompete talin for the binding to phosphorylated beta2 integrin. X-ray crystallographic data clearly explained how phosphorylation eliminated filamin binding and induced 14-3-3 protein binding. Filamin knockdown in T cells led to an increase in stimulated cell adhesion to ICAM-1-coated surfaces. Our results suggest that the phosphorylation of beta2 integrins on Thr758 acts as a molecular switch to inhibit filamin binding and allow 14-3-3 protein binding to the integrin cytoplasmic domain, thereby modulating T-cell adhesion."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2007-12-127795"xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2007-12-127795"xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Aatonen M."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Aatonen M."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Fagerholm S.C."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Fagerholm S.C."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Gahmberg C.G."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Gahmberg C.G."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Kiema T."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Kiema T."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Nurmi S.M."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Nurmi S.M."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Nurminen E."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Nurminen E."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Strandin T."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Strandin T."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Takala H."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Takala H."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Takatalo M."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Takatalo M."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Ylaenne J."xsd:string |
http://purl.uniprot.org/citations/18550856 | http://purl.uniprot.org/core/author | "Ylaenne J."xsd:string |