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http://purl.uniprot.org/citations/23460737http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23460737http://www.w3.org/2000/01/rdf-schema#comment"Thymocyte-expressed molecule involved in selection (THEMIS) is a recently identified regulator of thymocyte positive selection. THEMIS's mechanism of action is unknown, and whether it has a role in TCR-proximal signaling is controversial. In this article, we show that THEMIS and the adapter molecule growth factor receptor-bound protein 2 (GRB2) associate constitutively through binding of a conserved PxRPxK motif within the proline-rich region 1 of THEMIS to the C-terminal SH3-domain of GRB2. This association is indispensable for THEMIS recruitment to the immunological synapse via the transmembrane adapter linker for activation of T cells (LAT) and for THEMIS phosphorylation by Lck and ZAP-70. Two major sites of tyrosine phosphorylation were mapped to a YY-motif close to proline-rich region 1. The YY-motif was crucial for GRB2 binding, suggesting that this region of THEMIS might control local phosphorylation-dependent conformational changes important for THEMIS function. Finally, THEMIS binding to GRB2 was required for thymocyte development. Our data firmly assign THEMIS to the TCR-proximal signaling cascade as a participant in the LAT signalosome and suggest that the THEMIS-GRB2 complex might be involved in shaping the nature of Ras signaling, thereby governing thymic selection."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.org/dc/terms/identifier"doi:10.4049/jimmunol.1203389"xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/author"Fu G."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/author"Feller S.M."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/author"Simister P.C."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/author"Acuto O."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/author"Paster W."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/author"Brockmeyer C."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/author"Gascoigne N.R."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/author"Wulfing C."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/author"Hoerter J.A."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/author"Martinez-Riano A."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/author"de Wet B."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/name"J Immunol"xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/pages"3749-3756"xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/title"GRB2-mediated recruitment of THEMIS to LAT is essential for thymocyte development."xsd:string
http://purl.uniprot.org/citations/23460737http://purl.uniprot.org/core/volume"190"xsd:string
http://purl.uniprot.org/citations/23460737http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23460737
http://purl.uniprot.org/citations/23460737http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/23460737
http://purl.uniprot.org/uniprot/#_E0CY68-mappedCitation-23460737http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23460737
http://purl.uniprot.org/uniprot/#_E0CYT7-mappedCitation-23460737http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23460737
http://purl.uniprot.org/uniprot/#_A0A384ME16-mappedCitation-23460737http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23460737
http://purl.uniprot.org/uniprot/#_B0LPF3-mappedCitation-23460737http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23460737