{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:43:50Z","timestamp":1781109830855,"version":"3.54.1"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,5,5]]},"abstract":"<jats:p>The Wiskott-Aldrich syndrome (WAS) interacting protein (WIP) stabilizes the WAS protein (WASP), the product of the gene mutated in WAS. WIP-deficient T cells have low WASP levels, limiting the usefulness of WIP KO mice in defining the role of WIP in T cell function. To define this role, we compared WIP\/WASP double KO (DKO) mice to WASP KO mice on DO11.10 background. T cell development was normal in both strains, but peripheral T cell numbers were significantly decreased in DKO mice. WASP KO T cells proliferated and secreted IL-2 normally in response to OVA peptide (OVAp). In contrast, T cells from DKO mice proliferated poorly in response to OVAp in vitro, and cutaneous hapten hypersensitivity was deficient in these mice. DKO T cells up-regulated CD25 expression and secreted normal amounts of IL-2 after antigen stimulation, but had defective response to IL-2, evidenced by failure to further up-regulate CD25 expression, phosphorylate STAT5, and induce expression of STAT5-dependent genes. DKO, but not WASP KO, T cells had a disrupted subcortical actin cytoskeleton and impaired actin polymerization after T cell antigen receptor (TCR) ligation. These results indicate that WIP is essential for IL-2 signaling and responsiveness in T cells, possibly because of its critical role in TCR-triggered actin cytoskeletal reorganization.<\/jats:p>","DOI":"10.1073\/pnas.0806410106","type":"journal-article","created":{"date-parts":[[2009,4,9]],"date-time":"2009-04-09T21:51:56Z","timestamp":1239313916000},"page":"7519-7524","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["WIP is critical for T cell responsiveness to IL-2"],"prefix":"10.1073","volume":"106","author":[{"given":"Severine","family":"Le Bras","sequence":"first","affiliation":[{"name":"Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Massaad","sequence":"additional","affiliation":[{"name":"Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Koduru","sequence":"additional","affiliation":[{"name":"Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko K.","family":"Oyoshi","sequence":"additional","affiliation":[{"name":"Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hartwig","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Brigham and Women's Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raif S.","family":"Geha","sequence":"additional","affiliation":[{"name":"Division of Immunology, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,5,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2069"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.02.005"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80590-7"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.9.1329"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00728-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.03.037"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.1.33"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.04.015"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh310"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14671"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00268-6"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxl135"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.10.037"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/35074551"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.3.1658"},{"key":"e_1_3_3_16_2","doi-asserted-by":"crossref","first-page":"4383","DOI":"10.4049\/jimmunol.151.8.4383","article-title":"T cells of patients with the Wiskott\u2013Aldrich 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\u2013Aldrich syndrome have a restricted defect in proliferative responses. J Immunol 151, 4383\u20134390 (1993).","journal-title":"J Immunol"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.8.3089"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2003.01668.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.43"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-06-2332"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-096875"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.2.1135"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1332"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(20000101)76:1<37::AID-JCB5>3.0.CO;2-6"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80025-4"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80389-1"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1885"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/10799890600567372"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00855"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.04.001"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022619199"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.12.079"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0806410106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T16:15:42Z","timestamp":1684944942000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0806410106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,5,5]]},"references-count":32,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2009,5,5]]}},"alternative-id":["10.1073\/pnas.0806410106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0806410106","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,5,5]]},"assertion":[{"value":"2008-07-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}