{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:29:31Z","timestamp":1789644571094,"version":"4.0.0"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,5]],"date-time":"2015-12-05T00:00:00Z","timestamp":1449273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatrics International"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Wiskott\u2013Aldrich syndrome (WAS) is an X\u2010linked primary immunodeficiency disease characterized by recurrent infection, thrombocytopenia, and eczema. The gene responsible for X\u2010linked WAS encodes the Wiskott\u2013Aldrich syndrome protein (WASP), which is expressed in hematopoietic cells and which regulates T\u2010cell activation and cytoskeletal reorganization in T\u2010cell receptor (TCR) signaling. Here, I review my recent research on WASP and the WASP\u2010interacting protein (WIP) complex in T cells. I and my colleagues first established a diagnostic screening method using flow cytometry and genetic analysis, and elucidated the molecular pathogenesis in WAS patients with unique clinical manifestations. We investigated the mechanisms by which WASP is recruited to lipid rafts following TCR stimulation and to immunological synapses between antigen\u2010presenting cells and T cells. Subsequently, we elucidated the molecular mechanisms by which WASP is degraded by calpain and ubiquitinated by Cbl\u2010family proteins, which terminate WASP activation. More importantly, we found that WIP plays a critical role in WASP stability in T cells. These results provide new insights into the molecular pathogenesis of X\u2010linked WAS and have facilitated the identification of WIP deficiency as an autosomal recessive form of WAS.<\/jats:p>","DOI":"10.1111\/ped.12819","type":"journal-article","created":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T22:27:09Z","timestamp":1441232829000},"page":"4-7","source":"Crossref","is-referenced-by-count":17,"title":["WASP\u2013WIP complex in the molecular pathogenesis of Wiskott\u2013Aldrich syndrome"],"prefix":"10.1111","volume":"58","author":[{"given":"Yoji","family":"Sasahara","sequence":"first","affiliation":[{"name":"Department of Pediatrics Tohoku University Graduate School of Medicine  Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12049"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-008-8086-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004310050005"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1182\/blood.V95.3.1110","article-title":"X\u2010linked thrombocytopenia identified by flow cytometric demonstration of defective Wiskott\u2010Aldrich syndrome protein in lymphocytes","volume":"95","author":"Kanegane H","year":"2000","journal-title":"Blood"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(01)00549-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/08880019809014019"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1111\/j.1651-2227.2001.tb01589.x","article-title":"Epstein\u2010Barr virus\u2010associated Hodgkin's disease in a patient with Wiskott\u2010Aldrich syndrome","volume":"90","author":"Sasahara Y","year":"2011","journal-title":"Acta Paediatr."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0388"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20308"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00360-6"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00728-1"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162376099"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030652"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610275104"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.03.046"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062324"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxt072"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110896"},{"key":"e_1_2_7_20_1","article-title":"Analyses of genetic and clinical parameters for screening patients with inherited thrombocytopenia with small or normal\u2010sized platelets","author":"Ouchi\u2010Uchiyama M","journal-title":"Pediatr. Blood Cancer"}],"container-title":["Pediatrics International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fped.12819","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fped.12819","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ped.12819","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T03:17:36Z","timestamp":1694661456000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ped.12819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,5]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1111\/ped.12819"],"URL":"https:\/\/doi.org\/10.1111\/ped.12819","archive":["Portico"],"relation":{},"ISSN":["1328-8067","1442-200X"],"issn-type":[{"value":"1328-8067","type":"print"},{"value":"1442-200X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,5]]}}}