ABSTRACT SAP (or SH2D1A), an adaptor-like molecule expressed in immune cells, is composed almost exclusively of a Src homology 2 (SH2) domain1,2,3,4. In humans, SAP is mutated and either

absent or non-functional in X-linked lymphoproliferative (XLP) syndrome, a disease characterized by an inappropriate response to Epstein-Barr virus (EBV) infection5. Through its SH2 domain,

SAP associates with tyrosines in the cytoplasmic domain of the SLAM family of immune cell receptors, and is absolutely required for the function of these receptors1,6,7,8,9,10. This property

results from the ability of SAP to promote the selective recruitment and activation of FynT, a cytoplasmic Src-related protein tyrosine kinase (PTK)8. Here, we demonstrate that SAP operates

in which an adaptor molecule composed only of an SH2 domain links a receptor devoid of intrinsic catalytic activity to the kinase required for its function. Access through your institution

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OTHERS STRUCTURAL AND FUNCTIONAL ANALYSIS OF TARGET RECOGNITION BY THE LYMPHOCYTE ADAPTOR PROTEIN LNK Article Open access 20 October 2021 HACS1 SIGNALING ADAPTOR PROTEIN RECOGNIZES A MOTIF

IN THE PAIRED IMMUNOGLOBULIN RECEPTOR B CYTOPLASMIC DOMAIN Article Open access 13 November 2020 SH3-DOMAIN MUTATIONS SELECTIVELY DISRUPT CSK HOMODIMERIZATION OR PTPN22 BINDING Article Open

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Supported by grants from the CANVAC National Centre of Excellence, the National Cancer Institute of Canada and the Canadian Institutes of Health Research (to A.V.), the Institut National de

la Santé et de la Recherche Médicale and the Association pour la Recherche sur le Cancer (France) (to S.L.). S.L. held a Fellowship from the Medical Research Council of Canada. He is now a

Scientist from the Centre National de la Recherche Scientifique (France). A.V. is a Senior Investigator of the Canadian Institutes of Health Research and holds a Canada Research Chair.

AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Laboratory of Molecular Oncology, Clinical Research Institute of Montreal, Montréal, H2W 1R7, Québec, Canada Sylvain Latour, Romain Roncagalli, 

Riyan Chen, Marcin Bakinowski, Xiaochu Shi, Dominique Davidson & André Veillette * Unité INSERM U429, Hôpital Necker Enfants-Malades, Paris, France Sylvain Latour * Program in Molecular

Biology, University of Montréal, Montréal, H2W 1R7, Québec, Canada Romain Roncagalli & André Veillette * Department of Medicine, University of Montréal, Montréal, H2W 1R7, Québec, Canada

André Veillette * National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, MD, USA Pamela L. Schwartzberg * Department of Biochemistry, McGill University,

Montréal, H3G 1Y6, Québec, Canada André Veillette * Departments of Microbiology and Immunology, McGill University, Montréal, H3G 1Y6, Québec, Canada André Veillette * Department of Medicine,

McGill University, Montréal, H3G 1Y6, Québec, Canada André Veillette Authors * Sylvain Latour View author publications You can also search for this author inPubMed Google Scholar * Romain

Roncagalli View author publications You can also search for this author inPubMed Google Scholar * Riyan Chen View author publications You can also search for this author inPubMed Google

Scholar * Marcin Bakinowski View author publications You can also search for this author inPubMed Google Scholar * Xiaochu Shi View author publications You can also search for this author

inPubMed Google Scholar * Pamela L. Schwartzberg View author publications You can also search for this author inPubMed Google Scholar * Dominique Davidson View author publications You can

also search for this author inPubMed Google Scholar * André Veillette View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence

to André Veillette. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE

THIS ARTICLE Latour, S., Roncagalli, R., Chen, R. _et al._ Binding of SAP SH2 domain to FynT SH3 domain reveals a novel mechanism of receptor signalling in immune regulation. _Nat Cell Biol_

5, 149–154 (2003). https://doi.org/10.1038/ncb919 Download citation * Received: 03 September 2002 * Revised: 09 October 2002 * Accepted: 28 October 2002 * Published: 27 January 2003 * Issue

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