{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:45:56Z","timestamp":1791323156295,"version":"4.3.1"},"reference-count":71,"publisher":"Rockefeller University Press","issue":"9","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,11,1]]},"abstract":"<jats:p>The Wiskott-Aldrich syndrome protein (WASp) has been implicated in modulation of lymphocyte activation and cytoskeletal reorganization. To address the mechanisms whereby WASp subserves such functions, we have examined WASp roles in lymphocyte development and activation using mice carrying a WAS null allele (WAS\u2212\/\u2212). Enumeration of hemopoietic cells in these animals revealed total numbers of thymocytes, peripheral B and T lymphocytes, and platelets to be significantly diminished relative to wild-type mice. In the thymus, this abnormality was associated with impaired progression from the CD44\u2212CD25+ to the CD44\u2212CD25\u2212 stage of differentiation. WASp-deficient thymocytes and T cells also exhibited impaired proliferation and interleukin (IL)-2 production in response to T cell antigen receptor (TCR) stimulation, but proliferated normally in response to phorbol ester\/ionomycin. This defect in TCR signaling was associated with a reduction in TCR-evoked upregulation of the early activation marker CD69 and in TCR-triggered apoptosis. While induction of TCR-\u03b6, ZAP70, and total protein tyrosine phosphorylation as well as mitogen-activated protein kinase (MAPK) and stress-activated protein\/c-Jun NH2-terminal kinase (SAPK\/JNK) activation appeared normal in TCR-stimulated WAS\u2212\/\u2212 cells, TCR-evoked increases in intracellular calcium concentration were decreased in WASp-deficient relative to wild-type cells. WAS\u2212\/\u2212 lymphocytes also manifested a marked reduction in actin polymerization and both antigen receptor capping and endocytosis after TCR stimulation, whereas WAS\u2212\/\u2212 neutrophils exhibited reduced phagocytic activity. Together, these results provide evidence of roles for WASp in driving lymphocyte development, as well as in the translation of antigen receptor stimulation to proliferative or apoptotic responses, cytokine production, and cytoskeletal rearrangement. The data also reveal a role for WASp in modulating endocytosis and phagocytosis and, accordingly, suggest that the immune deficit conferred by WASp deficiency reflects the disruption of a broad range of cellular behaviors.<\/jats:p>","DOI":"10.1084\/jem.190.9.1329","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1329-1342","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":297,"title":["Antigen Receptor\u2013Induced Activation and Cytoskeletal Rearrangement Are Impaired in Wiskott-Aldrich Syndrome Protein\u2013Deficient Lymphocytes"],"prefix":"10.1084","volume":"190","author":[{"given":"Jinyi","family":"Zhang","sequence":"first","affiliation":[{"name":"aDepartment of Medicine, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"bDepartment of Immunology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"cDepartment of Medical Genetics and Microbiology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"hSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amro","family":"Shehabeldin","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"bDepartment of Immunology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"cDepartment of Medical Genetics and Microbiology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"hSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis A.G.","family":"da Cruz","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"bDepartment of Immunology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"cDepartment of Medical Genetics and Microbiology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"hSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Butler","sequence":"additional","affiliation":[{"name":"dDepartment of Biochemistry, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"gDivision of Cell Biology, Research Institute, Hospital for Sick Children"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ally-Khan","family":"Somani","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"bDepartment of Immunology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"cDepartment of Medical Genetics and Microbiology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"hSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"McGavin","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"bDepartment of Immunology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"cDepartment of Medical Genetics and Microbiology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"hSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivona","family":"Kozieradzki","sequence":"additional","affiliation":[{"name":"bDepartment of Immunology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"eDepartment of Medical Biophysics, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"fAmgen Institute, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio O.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"bDepartment of Immunology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"eDepartment of Medical Biophysics, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"fAmgen Institute, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andras","family":"Nagy","sequence":"additional","affiliation":[{"name":"cDepartment of Medical Genetics and Microbiology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"hSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Grinstein","sequence":"additional","affiliation":[{"name":"dDepartment of Biochemistry, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"gDivision of Cell Biology, Research Institute, Hospital for Sick Children"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef M.","family":"Penninger","sequence":"additional","affiliation":[{"name":"bDepartment of Immunology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"eDepartment of Medical Biophysics, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"fAmgen Institute, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Siminovitch","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"bDepartment of Immunology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"cDepartment of Medical Genetics and Microbiology, University of Toronto, Ontario, Canada M5G 1X5"},{"name":"hSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1999,11,1]]},"reference":[{"key":"2023072508583340700_R1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1542\/peds.13.2.133","article-title":"Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea","volume":"13","author":"Aldrich","year":"1954","journal-title":"Paediatrics."},{"key":"2023072508583340700_R2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/0002-9343(68)90051-X","article-title":"The Wiskott-Aldrich syndromean immunologic deficiency disease involving the afferent limb of immunity","volume":"44","author":"Cooper","year":"1968","journal-title":"Am. J. Med."},{"key":"2023072508583340700_R3","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1182\/blood.V55.2.243.243","article-title":"The Wiskott-Aldrich syndromestudies of lymphocytes, granulocytes, and platelets","volume":"55","author":"Ochs","year":"1980","journal-title":"Blood."},{"key":"2023072508583340700_R4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0008-8749(75)90204-X","article-title":"The Wiskott-Aldrich syndrome. Immunologic studies in nine patients and selected family members","volume":"19","author":"Spitler","year":"1975","journal-title":"Cell. Immunol."},{"key":"2023072508583340700_R5","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.1365-2141.1969.tb01383.x","article-title":"Wiskott-Aldrich syndromequalitative platelet defects and short platelet survival","volume":"17","author":"Grottum","year":"1969","journal-title":"Br. J. Haematol."},{"key":"2023072508583340700_R6","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/S0022-3476(05)82002-5","article-title":"A multiinstitutional survey of the Wiskott-Aldrich syndrome","volume":"125","author":"Sullivan","year":"1994","journal-title":"J. Pediatr."},{"key":"2023072508583340700_R7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0197-1859(94)90039-6","article-title":"Molecular characterization of the X-linked immunodeficiency diseases","volume":"14","author":"Greer","year":"1994","journal-title":"Clin. Immunol. News."},{"key":"2023072508583340700_R8","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1111\/j.1365-2141.1986.tb04097.x","article-title":"The Wiskott-Aldrich syndromestudies of platelets, basophils and polymorphonuclear leucocytes","volume":"62","author":"Marone","year":"1986","journal-title":"Br. J. Haematol."},{"key":"2023072508583340700_R9","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1172\/JCI116006","article-title":"Evidence for defective transmembrane signaling in B cells from patients with Wiskott-Aldrich syndrome","volume":"90","author":"Simon","year":"1992","journal-title":"J. Clin. Invest."},{"key":"2023072508583340700_R10","doi-asserted-by":"crossref","first-page":"4383","DOI":"10.4049\/jimmunol.151.8.4383","article-title":"T cells of patients with the Wiskott-Aldrich syndrome have a restricted defect in proliferative responses","volume":"151","author":"Molina","year":"1993","journal-title":"J. Immunol."},{"key":"2023072508583340700_R11","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1046\/j.1365-2141.1997.1132938.x","article-title":"Flow cytometric analysis of platelets from children with the Wiskott-Aldrich syndrome reveals defects in platelet development activation and structure","volume":"97","author":"Semple","year":"1997","journal-title":"Br. J. Haematol"},{"key":"2023072508583340700_R12","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1182\/blood.V90.8.3089","article-title":"Defective actin organization and polymerization of Wiskott-Aldrich T cells in response to CD3-mediated stimulation","volume":"90","author":"Gallego","year":"1997","journal-title":"Blood."},{"key":"2023072508583340700_R13","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1182\/blood.V68.6.1329.1329","article-title":"Morphological abnormalities in the lymphocytes of patients with the Wiskott-Aldrich syndrome","volume":"68","author":"Kenney","year":"1986","journal-title":"Blood."},{"key":"2023072508583340700_R14","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1046\/j.1365-2141.1998.00767.x","article-title":"Chemotaxis of macrophages is abolished in the Wiskott-Aldrich syndrome","volume":"101","author":"Zicha","year":"1998","journal-title":"Br. J. Haematol."},{"key":"2023072508583340700_R15","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.4049\/jimmunol.161.2.1026","article-title":"Monocytes from Wiskott-Aldrich patients display reduced chemotaxis and lack of cell polarization in response to monocyte chemoattractant protein-1 and formyl-methionyl-leucyl-phenylalanine","volume":"161","author":"Badolato","year":"1998","journal-title":"J. Immunol."},{"key":"2023072508583340700_R16","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1182\/blood.V56.6.1048.1048","article-title":"Wiskott-Aldrich syndromecellular impairments and their implication for carrier detection","volume":"56","author":"Prchal","year":"1980","journal-title":"Blood."},{"key":"2023072508583340700_R17","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/0888-7543(89)90315-7","article-title":"Y-chromosome inactivation in the Wiskott-Aldrich syndromea marker for detection in the carrier state and identification of cell lineages expressing the WAS gene defect","volume":"4","author":"Greer","year":"1989","journal-title":"Genomics."},{"key":"2023072508583340700_R18","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/0090-1229(89)90179-7","article-title":"The increase of non-MHC-restricted cytotoxic cells (\u03b3\/\u03b4-TCR-bearing T cells or NK cells) and the abnormal differentiation of B cells in Wiskott-Aldrich syndrome","volume":"52","author":"Morio","year":"1989","journal-title":"Clin. Immunol. Immunopathol."},{"key":"2023072508583340700_R19","doi-asserted-by":"crossref","first-page":"2966","DOI":"10.4049\/jimmunol.133.6.2966","article-title":"Newborn and Wiskott-Aldrich patient B cells can be activated by TNP-Brucella abortusevidence that TNP-Brucella abortus behaves as a T-independent type I antigen in humans","volume":"133","author":"Golding","year":"1984","journal-title":"J. Immunol."},{"key":"2023072508583340700_R20","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1139\/o89-081","article-title":"Altered expression of leucocyte sialoglycoprotein in Wiskott-Aldrich syndrome is associated with a specific defect in O-glycosylation","volume":"67","author":"Greer","year":"1989","journal-title":"Biochem. Cell Biol."},{"key":"2023072508583340700_R21","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1084\/jem.173.6.1501","article-title":"Altered O-glycan synthesis in lymphocytes from patients with Wiskott-Aldrich syndrome","volume":"173","author":"Piller","year":"1991","journal-title":"J. Exp. Med."},{"key":"2023072508583340700_R22","doi-asserted-by":"crossref","first-page":"6280","DOI":"10.1016\/S0021-9258(18)38115-8","article-title":"Aberrant O-linked oligosaccharide biosynthesis in lymphocytes and platelets from patients with the Wiskott-Aldrich syndrome","volume":"266","author":"Higgins","year":"1991","journal-title":"J. Biol. Chem."},{"key":"2023072508583340700_R23","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/0092-8674(94)90528-2","article-title":"Isolation of a novel gene mutated in Wiskott-Aldrich syndrome","volume":"78","author":"Derry","year":"1994","journal-title":"Cell."},{"key":"2023072508583340700_R24","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1182\/blood.V90.1.70","article-title":"Expression of Wiskott-Aldrich syndrome protein (WASp) gene during haemopoietic differentiation","volume":"90","author":"Parolini","year":"1997","journal-title":"Blood."},{"key":"2023072508583340700_R25","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1172\/JCI118712","article-title":"Studies of the expression of the Wiskott-Aldrich syndrome protein","volume":"97","author":"Stewart","year":"1996","journal-title":"J. Clin. Invest."},{"key":"2023072508583340700_R26","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1006\/bbrc.1997.8064","article-title":"Direct binding of the verprolin-homology domain in N-WASp to \u201cactin\u201d is essential for cytoskeletal reorganization","volume":"243","author":"Miki","year":"1998","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"2023072508583340700_R27","doi-asserted-by":"crossref","first-page":"5307","DOI":"10.1021\/bi00317a032","article-title":"Cofilin, a protein in porcine brain that binds to actin filaments and inhibits their interactions with myosin and tropo-myosin","volume":"23","author":"Nishida","year":"1984","journal-title":"Biochemistry."},{"key":"2023072508583340700_R28","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S0960-9822(02)00423-2","article-title":"Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder, Wiskott-Aldrich syndrome","volume":"6","author":"Aspenstr\u00f6m","year":"1995","journal-title":"Curr. Biol."},{"key":"2023072508583340700_R29","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0092-8674(95)90370-4","article-title":"Rho, rac and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia and filopodia","volume":"81","author":"Nobes","year":"1995","journal-title":"Cell."},{"key":"2023072508583340700_R30","doi-asserted-by":"crossref","first-page":"5027","DOI":"10.1073\/pnas.92.11.5027","article-title":"Regulation of the polarization of T cells toward antigen-presenting cells by Ras-related GTPase CDC42","volume":"92","author":"Stowers","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072508583340700_R31","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S0092-8674(00)81050-8","article-title":"Wiskott-Aldrich syndrome protein, a novel effector for the GTPase cdc42Hs, is implicated in actin polymerization","volume":"84","author":"Symons","year":"1996","journal-title":"Cell."},{"key":"2023072508583340700_R32","first-page":"195","article-title":"Tyrosine kinase signaling regulates Wiskott-Aldrich syndrome protein function, which is essential for megakaryocyte differentiation","volume":"8","author":"Miki","year":"1997","journal-title":"Cell Growth Differ."},{"key":"2023072508583340700_R33","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1083\/jcb.136.3.649","article-title":"Bee1, a yeast protein with homology to Wiskott-Aldrich syndrome protein, is critical for the assembly of cortical actin cytoskeleton","volume":"136","author":"Li","year":"1997","journal-title":"J. Cell Biol."},{"key":"2023072508583340700_R34","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/34208","article-title":"Induction of filopodium formation by a WASp-related actin-depolymerizing protein N-WASp","volume":"39","author":"Miki","year":"1998","journal-title":"Nature."},{"key":"2023072508583340700_R35","doi-asserted-by":"crossref","first-page":"6932","DOI":"10.1093\/emboj\/17.23.6932","article-title":"WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac","volume":"17","author":"Miki","year":"1998","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072508583340700_R36","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1083\/jcb.142.5.1325","article-title":"SCAR, a WASp-related protein, isolated as a suppressor of receptor defects in late Dictyostelium development","volume":"142","author":"Bear","year":"1998","journal-title":"J. Cell Biol."},{"key":"2023072508583340700_R37","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/S0960-9822(98)00015-3","article-title":"Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2\/3 complex","volume":"8","author":"Machesky","year":"1998","journal-title":"Curr. Biol"},{"key":"2023072508583340700_R38","doi-asserted-by":"crossref","first-page":"5326","DOI":"10.1002\/j.1460-2075.1996.tb00917.x","article-title":"N-WASP, a novel actin-depolymerization protein, regulates the cortical cytoskeletal rearrangement in a PIP2-dependent manner downstream of tyrosine kinase","volume":"15","author":"Miki","year":"1996","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072508583340700_R39","doi-asserted-by":"crossref","first-page":"5725","DOI":"10.1128\/MCB.15.10.5725","article-title":"Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains","volume":"15","author":"Rivero-Lezcano","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"2023072508583340700_R40","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1093\/emboj\/17.19.5647","article-title":"A Nck-Pak1 signaling module is required for T-cell receptor-mediated activation of NF-AT, but not of JNK","volume":"17","author":"Yablonski","year":"1998","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072508583340700_R41","doi-asserted-by":"crossref","first-page":"25646","DOI":"10.1074\/jbc.271.41.25646","article-title":"Identification of Itk\/Tsk Src homology 3 domain ligands","volume":"271","author":"Bunnel","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2023072508583340700_R42","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/S0960-9822(02)00642-5","article-title":"Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-SRC family protein-tyrosine kinases","volume":"6","author":"Banin","year":"1996","journal-title":"Curr. Biol."},{"key":"2023072508583340700_R43","doi-asserted-by":"crossref","first-page":"3791","DOI":"10.4049\/jimmunol.157.9.3791","article-title":"Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways","volume":"157","author":"Cory","year":"1996","journal-title":"J. Immunol."},{"key":"2023072508583340700_R44","doi-asserted-by":"crossref","first-page":"26291","DOI":"10.1074\/jbc.271.42.26291","article-title":"Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains","volume":"271","author":"Tinan","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2023072508583340700_R45","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S1074-7613(00)80590-7","article-title":"Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation","volume":"9","author":"Snapper","year":"1998","journal-title":"Immunity"},{"key":"2023072508583340700_R46","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/0092-8674(91)90011-M","article-title":"Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene","volume":"65","author":"Tybulewicz","year":"1991","journal-title":"Cell."},{"key":"2023072508583340700_R47","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0091-679X(08)61585-X","article-title":"Embryonal stem cells, creating transgenic animals","volume":"57","author":"Pirity","year":"1998","journal-title":"Methods Cell Biol."},{"key":"2023072508583340700_R48","doi-asserted-by":"crossref","first-page":"4528","DOI":"10.1073\/pnas.90.10.4528","article-title":"RAG-2-deficient blastocyst complementationan assay of gene function in lymphocyte development","volume":"90","author":"Chen","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072508583340700_R49","doi-asserted-by":"crossref","first-page":"952","DOI":"10.4049\/jimmunol.137.3.952","article-title":"Heterogeneity among T cells in intracellular free calcium responses after mitogen stimulation with PHA or anti-CD3. Simultaneous use of indo-1 and immunofluorescence with flow cytometry","volume":"137","author":"Rabinovitch","year":"1986","journal-title":"J. Immunol."},{"key":"2023072508583340700_R50","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/379081a0","article-title":"Defective thymocyte proliferation and IL-2 production in transgenic mice expressing a dominant-negative form of CREB","volume":"379","author":"Barton","year":"1996","journal-title":"Nature."},{"key":"2023072508583340700_R51","doi-asserted-by":"crossref","first-page":"4244","DOI":"10.4049\/jimmunol.150.10.4244","article-title":"A developmental pathway involving four phenotypically and functionally distinct subsets of CD3\u2212CD4\u2212CD8\u2212 triple-negative adult mouse thymocytes defined by CD44 and CD25","volume":"150","author":"Godfrey","year":"1993","journal-title":"J. Immunol."},{"key":"2023072508583340700_R52","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1084\/jem.183.4.1707","article-title":"CD45-null transgenic mice reveal a positive regulatory role for CD45 and early thymocyte development, in the selection of CD4+ CD8+ thymocytes and B cell maturation","volume":"183","author":"Byth","year":"1996","journal-title":"J. Exp. Med."},{"key":"2023072508583340700_R53","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1002\/j.1460-2075.1993.tb05812.x","article-title":"A dominant-negative transgene defines a role for p56lck in thymocytes","volume":"12","author":"Levin","year":"1993","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072508583340700_R54","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/S0960-9822(98)70224-6","article-title":"Vav is a regulator of cytoskeleton reorganization mediated by the T-cell receptor","volume":"8","author":"Fischer","year":"1998","journal-title":"Curr. Biol."},{"key":"2023072508583340700_R55","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S1074-7613(00)80367-2","article-title":"A requirement for the Rho-family GTP exchange factor Vav in positive and negative selection of thymocytes","volume":"7","author":"Turner","year":"1997","journal-title":"Immunity."},{"key":"2023072508583340700_R56","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.7973703","article-title":"Analysis and expression of a cloned pre-T receptor gene","volume":"266","author":"Saint-Ruf","year":"1994","journal-title":"Science."},{"key":"2023072508583340700_R57","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/eji.1830230326","article-title":"CD69 expression during selection and maturation of CD4+CD8+ thymocytes","volume":"23","author":"Swat","year":"1993","journal-title":"Eur. J. Immunol."},{"key":"2023072508583340700_R58","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.4049\/jimmunol.142.6.1854","article-title":"Leu23 induction as an early marker of functional CD3\/T cell antigen receptor triggering. Requirement for receptor cross-linking, prolonged elevation of intracellular [Ca++] and stimulation of protein kinase C","volume":"142","author":"Testi","year":"1989","journal-title":"J. Immunol."},{"key":"2023072508583340700_R59","doi-asserted-by":"crossref","first-page":"11398","DOI":"10.1016\/S0021-9258(18)67398-3","article-title":"Novel blockade by brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes","volume":"261","author":"Misumi","year":"1986","journal-title":"J. Biol. Chem."},{"key":"2023072508583340700_R60","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1182\/blood.V86.4.1408.bloodjournal8641408","article-title":"Direct demonstration of cytokine synthesis heterogeneity among human memory\/effector T cells by flow cytometry","volume":"86","author":"Picker","year":"1995","journal-title":"Blood."},{"key":"2023072508583340700_R61","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.4049\/jimmunol.128.3.1198","article-title":"Ligand-induced association of surface immunoglobulin with the detergent-insoluble cytoskeletal matrix of the B lymphocyte","volume":"128","author":"Braun","year":"1982","journal-title":"J. Immunol."},{"key":"2023072508583340700_R62","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S0960-9822(98)70396-3","article-title":"The WASp homologue Las17p functions with the WIP homologue End5p\/verprolin and is essential for endocytosis in yeast","volume":"8","author":"Naqvi","year":"1998","journal-title":"Curr. Biol"},{"key":"2023072508583340700_R63","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/374474a0","article-title":"Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes","volume":"374","author":"Fischer","year":"1995","journal-title":"Nature."},{"key":"2023072508583340700_R64","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/374467a0","article-title":"Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav","volume":"374","author":"Tarakhovsky","year":"1995","journal-title":"Nature."},{"key":"2023072508583340700_R65","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/374470a0","article-title":"Defective signaling through T- and B-cell antigen receptors in lymphoid cells lacking the Vav proto-oncogene","volume":"374","author":"Zhang","year":"1995","journal-title":"Nature."},{"key":"2023072508583340700_R66","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/385169a0","article-title":"Phosphotyrosine-dependent activation of Rac-1 GDP\/GTP exchange by the Vav proto-oncogene product","volume":"385","author":"Crespo","year":"1997","journal-title":"Nature."},{"key":"2023072508583340700_R67","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1128\/MCB.17.3.1346","article-title":"Lck regulates Vav activation of members of the Rho-family of GTPases","volume":"17","author":"Han","year":"1997","journal-title":"Mol. Cell Biol"},{"key":"2023072508583340700_R68","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S0092-8674(00)81608-6","article-title":"A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts","volume":"94","author":"Dustin","year":"1998","journal-title":"Cell."},{"key":"2023072508583340700_R69","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1126\/science.282.5397.2266","article-title":"A receptor\/cytoskeletal movement triggered by costimulation during T cell activation","volume":"282","author":"W\u00fclfing","year":"1998","journal-title":"Science"},{"key":"2023072508583340700_R70","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1084\/jem.181.2.577","article-title":"Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cell actin cytoskeleton","volume":"181","author":"Valitutti","year":"1995","journal-title":"J. Exp. Med"},{"key":"2023072508583340700_R71","doi-asserted-by":"crossref","first-page":"6302","DOI":"10.1073\/pnas.95.11.6302","article-title":"Visualizing the dynamics of T cell activationintracellular adhesion molecule 1 migrates rapidly to the T cell\/B cell interface and acts to sustain calcium levels","volume":"95","author":"W\u00fclfing","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/190\/9\/1329\/1696118\/99-1241.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/190\/9\/1329\/1696118\/99-1241.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T10:10:10Z","timestamp":1690279810000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/190\/9\/1329\/30000\/Antigen-Receptor-Induced-Activation-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,11,1]]},"references-count":71,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1999,11,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.190.9.1329","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,11,1]]}}}