| http://purl.uniprot.org/citations/16983070 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16983070 | http://www.w3.org/2000/01/rdf-schema#comment | "SLAM (signaling lymphocyte activation molecule)-associated protein (SAP) is a Src homology 2 (SH2) domain-containing adaptor expressed in T cells and natural killer cells. Its essential role in immune responses is underscored by the recent finding that mutations in SAP result in a rare but fatal X-linked lymphoproliferative disease (XLP). Although SAP is known to associate with SLAM-family receptors, the exact molecular mechanism by which SAP regulates lymphocyte signaling remains elusive. We here report that in T cells, SAP associates with the PAK-interacting exchange factor (PIX), a guanine nucleotide exchange factor (GEF) specific for Rac/Cdc42 GTPases. Moreover, SAP, PIX, and an activated form of Cdc42 form a complex in mammalian cells. We demonstrate that the SAP-PIX interaction is specific and is mediated by the C-terminal region of the SAP SH2 domain and the PIX SH3 domain. We further show that SAP is required for the recruitment of PIX to the SLAM-family receptors. Interestingly, overexpression of SAP, but not its homolog EAT-2, leads to a synergistic activation of nuclear factor of activating T cells (NFAT) in combination with a calcium signal in T cells. This SAP-mediated activation appears to be receptor-dependent and can be blocked by a dominant negative form of PIX. Taken together, our data strongly suggest that, in addition to the known SAP-interacting kinase Fyn, PIX may be another key player in SAP-mediated T cell activation."xsd:string |
| http://purl.uniprot.org/citations/16983070 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0606624103"xsd:string |
| http://purl.uniprot.org/citations/16983070 | http://purl.uniprot.org/core/author | "Luo Y."xsd:string |
| http://purl.uniprot.org/citations/16983070 | http://purl.uniprot.org/core/author | "Gu C."xsd:string |
| http://purl.uniprot.org/citations/16983070 | http://purl.uniprot.org/core/author | "Lin Z."xsd:string |
| http://purl.uniprot.org/citations/16983070 | http://purl.uniprot.org/core/author | "Sun X."xsd:string |
| http://purl.uniprot.org/citations/16983070 | http://purl.uniprot.org/core/author | "Wu J."xsd:string |
| http://purl.uniprot.org/citations/16983070 | http://purl.uniprot.org/core/author | "Tangye S.G."xsd:string |
| http://purl.uniprot.org/citations/16983070 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16983070 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/16983070 | http://purl.uniprot.org/core/pages | "14447-14452"xsd:string |
| http://purl.uniprot.org/citations/16983070 | http://purl.uniprot.org/core/title | "The X-linked lymphoproliferative disease gene product SAP associates with PAK-interacting exchange factor and participates in T cell activation."xsd:string |
| http://purl.uniprot.org/citations/16983070 | http://purl.uniprot.org/core/volume | "103"xsd:string |
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