ArticleProceedings of the National Academy of Sciences of the United States of America2006
The X-linked lymphoproliferative disease gene product SAP associates with PAK-interacting exchange factor and participates in T cell activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- 2B4/CD244 Signaling in Immune Regulation and Its Role in Infection, Cancer, and Immune Tolerance.ImmunoTargets and therapy · 2025Review
- Wiskott-Aldrich syndrome protein interacts and inhibits diacylglycerol kinase alpha promoting IL-2 induction.Frontiers in immunology · 2023Article
- Are Viral Infections Key Inducers of Autoimmune Diseases? Focus on Epstein-Barr Virus.Viruses · 2022Review
- T cell receptor (TCR) signaling in health and disease.Signal transduction and targeted therapy · 2021Review
- Diacylglycerol Kinase alpha in X Linked Lymphoproliferative Disease Type 1.International journal of molecular sciences · 2021Review
- Microarray profile of B cells from Graves' disease patients reveals biomarkers of proliferation.Endocrine connections · 2020Article
- NK cell recognition of hematopoietic cells by SLAM-SAP families.Cellular & molecular immunology · 2019Review
- Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Expanding functions of GIT Arf GTPase-activating proteins, PIX Rho guanine nucleotide exchange factors and GIT-PIX complexes.Journal of cell science · 2016Review
- The adaptor protein SAP directly associates with CD3ζ chain and regulates T cell receptor signaling.PloS one · 2012Article
- Article
- SAP-mediated inhibition of diacylglycerol kinase α regulates TCR-induced diacylglycerol signaling.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Review
- Measles virus glycoprotein-pseudotyped lentiviral vector-mediated gene transfer into quiescent lymphocytes requires binding to both SLAM and CD46 entry receptors.Journal of virology · 2011Article
- 2B4 utilizes ITAM-containing receptor complexes to initiate intracellular signaling and cytolysis.Molecular immunology · 2011Article
- Review
- Biochemical and genetic evidence for a SAP-PKC-theta interaction contributing to IL-4 regulation.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- SLAM family receptors and the SLAM-associated protein (SAP) modulate T cell functions.Seminars in immunopathology · 2010Review
- SLAM-family receptors: immune regulators with or without SAP-family adaptors.Cold Spring Harbor perspectives in biology · 2010Review
- Inhibition and activation by CD244 depends on CD2 and phospholipase C-gamma1.The Journal of biological chemistry · 2009Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.