{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:43:27Z","timestamp":1791164607688,"version":"4.1.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,9,15]]},"abstract":"<jats:p>The Wiskott-Aldrich syndrome protein (WASp) is a key cytoskeletal regulator in hematopoietic cells. Covalent modification of a conserved tyrosine by phosphorylation has emerged as an important potential determinant of activity, although the physiological significance remains uncertain. In a murine knockin model, mutation resulting in inability to phosphorylate Y293 (Y293F) mimicked many features of complete WASp-deficiency. Although a phosphomimicking mutant Y293E conferred enhanced actin-polymerization, the cellular phenotype was similar due to functional dysregulation. Furthermore, steady-state levels of Y293E-WASp were markedly reduced compared to wild-type WASp and Y293F-WASp, although partially recoverable by treatment of cells with proteasome inhibitors. Consequently, tyrosine phosphorylation plays a critical role in normal activation of WASp in vivo, and is indispensible for multiple tasks including proliferation, phagocytosis, chemotaxis, and assembly of adhesion structures. Furthermore, it may target WASp for proteasome-mediated degradation, thereby providing a default mechanism for self-limiting stimulation of the Arp2\/3 complex.<\/jats:p>","DOI":"10.1073\/pnas.0904346106","type":"journal-article","created":{"date-parts":[[2009,9,1]],"date-time":"2009-09-01T22:03:06Z","timestamp":1251842586000},"page":"15738-15743","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":48,"title":["Phosphorylation of WASp is a key regulator of activity and stability in vivo"],"prefix":"10.1073","volume":"106","author":[{"given":"Michael P.","family":"Blundell","sequence":"first","affiliation":[{"name":"Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom;"},{"name":"Great Ormond Street Hospital NHS Trust, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerben","family":"Bouma","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom;"},{"name":"Great Ormond Street Hospital NHS Trust, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao","family":"Metelo","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom;"},{"name":"Great Ormond Street Hospital NHS Trust, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austen","family":"Worth","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom;"},{"name":"Great Ormond Street Hospital NHS Trust, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Calle","sequence":"additional","affiliation":[{"name":"King's College London, Department of Haematological Medicine, The Rayne Institute, London SE5 9NU, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy A.","family":"Cowell","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom;"},{"name":"Great Ormond Street Hospital NHS Trust, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa S.","family":"Westerberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, GI Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale A.","family":"Moulding","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom;"},{"name":"Great Ormond Street Hospital NHS Trust, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Mirando","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom;"},{"name":"Great Ormond Street Hospital NHS Trust, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Kinnon","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom;"},{"name":"Great Ormond Street Hospital NHS Trust, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giles O.","family":"Cory","sequence":"additional","affiliation":[{"name":"Peninsula College of Medicine and Dentistry, Peninsula Medical School, Exeter EX1 2LU; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth E.","family":"Jones","sequence":"additional","affiliation":[{"name":"Randall Division of Cell and Molecular Biophysics, Kings College, London SE1 1UL, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott B.","family":"Snapper","sequence":"additional","affiliation":[{"name":"Department of Medicine, GI Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan O.","family":"Burns","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom;"},{"name":"Great Ormond Street Hospital NHS Trust, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Thrasher","sequence":"additional","affiliation":[{"name":"Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom;"},{"name":"Great Ormond Street Hospital NHS Trust, London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,9,15]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri884"},{"key":"e_1_3_3_2_2","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 IJ","year":"1993","unstructured":"IJ Molina, J Sancho, C Terhorst, FS Rosen, E Remold-O'Donnell, T cells of patients with the Wiskott-Aldrich syndrome have a restricted defect in proliferative responses. J Immunol 151, 4383\u20134390 (1993).","journal-title":"J Immunol"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.4.1142"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.8.4831"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00360-6"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-06-2332"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/35004513"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610275104"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01076-0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.10.037"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5492.801"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.6.1299"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.6.1311"},{"key":"e_1_3_3_14_2","first-page":"45115","article-title":"Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation","volume":"277","author":"Cory GO","year":"2002","unstructured":"GO Cory, R Garg, R Cramer, AJ Ridley, Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein. J Biol Chem 277, 45115\u201345121 (2002).","journal-title":"Wiskott-Aldrich Syndrome protein. J Biol Chem"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00139-4"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030976"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705999200"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608957200"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081773"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-1003"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-02-140715"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29539"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02939"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.9.2943.009k17_2943_2946"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2003.01668.x"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062324"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80590-7"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.38.27225"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2004.08.019"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/85886"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-01-010249"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07416.x"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00268-6"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00728-1"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704972200"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00324-6"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600586"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.43"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.20.2.199"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1439"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.2008.02069.x"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0904346106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T11:21:30Z","timestamp":1685100090000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0904346106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9,15]]},"references-count":41,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2009,9,15]]}},"alternative-id":["10.1073\/pnas.0904346106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0904346106","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1168247.630400","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,9,15]]},"assertion":[{"value":"2009-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-09-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}