{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:20:11Z","timestamp":1791843611655,"version":"4.3.4"},"reference-count":33,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,1,5]]},"abstract":"<jats:p>Involvement of the Wiskott-Aldrich syndrome protein (WASp) in promoting cell activation requires its release from autoinhibitory structural constraints and has been attributed to WASp association with activated cdc42. Here, however, we show that T cell development and T cell receptor (TCR)-induced proliferation and actin polymerization proceed normally in WASp\u2212\/\u2212 mice expressing a WASp transgene lacking the cdc42 binding domain. By contrast, mutation of tyrosine residue Y291, identified here as the major site of TCR-induced WASp tyrosine phosphorylation, abrogated induction of WASp tyrosine phosphorylation and its effector activities, including nuclear factor of activated T cell transcriptional activity, actin polymerization, and immunological synapse formation. TCR-induced WASp tyrosine phosphorylation was also disrupted in T cells lacking Fyn, a kinase shown here to bind, colocalize with, and phosphorylate WASp. By contrast, WASp was tyrosine dephosphorylated by protein tyrosine phosphatase (PTP)-PEST, a tyrosine phosphatase shown here to interact with WASp via proline, serine, threonine phosphatase interacting protein (PSTPIP)1 binding. Although Fyn enhanced WASp-mediated Arp2\/3 activation and was required for synapse formation, PTP-PEST combined with PSTPIP1 inhibited WASp-driven actin polymerization and synapse formation. These observations identify key roles for Fyn and PTP-PEST in regulating WASp and imply that inducible WASp tyrosine phosphorylation can occur independently of cdc42 binding, but unlike the cdc42 interaction, is absolutely required for WASp contributions to T cell activation.<\/jats:p>","DOI":"10.1084\/jem.20030976","type":"journal-article","created":{"date-parts":[[2004,1,5]],"date-time":"2004-01-05T20:08:10Z","timestamp":1073333290000},"page":"99-112","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":167,"title":["Fyn and PTP-PEST\u2013mediated Regulation of Wiskott-Aldrich Syndrome Protein (WASp) Tyrosine Phosphorylation Is Required for Coupling T Cell Antigen Receptor Engagement to WASp Effector Function and T Cell Activation"],"prefix":"10.1084","volume":"199","author":[{"given":"Karen","family":"Badour","sequence":"first","affiliation":[{"name":"aDepartment of Medicine, Department of Immunology, Department of Medical Genetics and Microbiology, and Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X5, Canada"},{"name":"bSamuel Lunenfeld and Toronto General Research Institutes, Mount Sinai Hospital and the University Health Network, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, Department of Immunology, Department of Medical Genetics and Microbiology, and Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X5, Canada"},{"name":"bSamuel Lunenfeld and Toronto General Research Institutes, Mount Sinai Hospital and the University Health Network, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Shi","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, Department of Immunology, Department of Medical Genetics and Microbiology, and Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X5, Canada"},{"name":"bSamuel Lunenfeld and Toronto General Research Institutes, Mount Sinai Hospital and the University Health Network, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Leng","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, Department of Immunology, Department of Medical Genetics and Microbiology, and Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X5, Canada"},{"name":"bSamuel Lunenfeld and Toronto General Research Institutes, Mount Sinai Hospital and the University Health Network, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Collins","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, Department of Immunology, Department of Medical Genetics and Microbiology, and Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X5, Canada"},{"name":"bSamuel Lunenfeld and Toronto General Research Institutes, Mount Sinai Hospital and the University Health Network, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Siminovitch","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, Department of Immunology, Department of Medical Genetics and Microbiology, and Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X5, Canada"},{"name":"bSamuel Lunenfeld and Toronto General Research Institutes, Mount Sinai Hospital and the University Health Network, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2004,1,5]]},"reference":[{"key":"2023072512184521400_BIB1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1034\/j.1600-065X.2003.00031.x","volume":"192","year":"2003","journal-title":"Immunol. 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