{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T07:51:33Z","timestamp":1767340293065},"reference-count":52,"publisher":"Proceedings of the National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,4,13]]},"abstract":"<jats:p>The mechanisms governing positive selection of T cells in the thymus are still incompletely understood. Here, we describe a<jats:italic>N<\/jats:italic>-ethyl-<jats:italic>N<\/jats:italic>-nitrosourea induced recessive mouse mutant,<jats:italic>Ms. T-less<\/jats:italic>, which lacks T cells in the peripheral blood because of a complete block of thymocyte development at the CD4<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>stage. Single nucleotide polymorphism mapping and candidate gene sequencing revealed a nonsense mutation in the inositol (1,4,5) trisphosphate 3 kinase B (<jats:italic>Itpkb<\/jats:italic>) gene in<jats:italic>Ms. T-less<\/jats:italic>mice. Accordingly,<jats:italic>Ms. T-less<\/jats:italic>thymocytes do not show detectable expression of Itpkb protein and have drastically reduced basal inositol (1,4,5) trisphosphate kinase activity. Itpkb converts inositol (1,4,5) trisphosphate to inositol (1,3,4,5) tetrakisphosphate, soluble second messengers that have been implicated in Ca<jats:sup>2+<\/jats:sup>signaling. Surprisingly, Ca<jats:sup>2+<\/jats:sup>responses show no significant differences between wild type (WT) and mutant thymocytes. However, extracellular signal-regulated kinase (Erk) activation in response to suboptimal antigen receptor stimulation is attenuated in<jats:italic>Ms. T-less<\/jats:italic>thymocytes, suggesting a role for<jats:italic>Itpkb<\/jats:italic>in linking T cell receptor signaling to efficient and sustained Erk activation.<\/jats:p>","DOI":"10.1073\/pnas.0306907101","type":"journal-article","created":{"date-parts":[[2004,4,3]],"date-time":"2004-04-03T02:53:25Z","timestamp":1080960805000},"page":"5604-5609","update-policy":"http:\/\/dx.doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":67,"title":["Inositol (1,4,5) trisphosphate 3 kinase B controls positive selection of T cells and modulates Erk activity"],"prefix":"10.1073","volume":"101","author":[{"given":"Ben G.","family":"Wen","sequence":"first","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}]},{"given":"Mathew T.","family":"Pletcher","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}]},{"given":"Masaki","family":"Warashina","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}]},{"given":"Sun Hui","family":"Choe","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}]},{"given":"Niusha","family":"Ziaee","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}]},{"given":"Tim","family":"Wiltshire","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}]},{"given":"Karsten","family":"Sauer","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}]},{"given":"Michael P.","family":"Cooke","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}]}],"member":"341","published-online":{"date-parts":[[2004,4,2]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141107"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/83118"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.259"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.092601.111357"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00199-6"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2002.6456"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.497"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2760(98)00131-3"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/35073015"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/35047115"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2157285"},{"key":"e_1_3_2_12_2","first-page":"343","volume":"2","year":"2000","unstructured":"Dewaste, V., Pouillon, V., Moreau, C., Shears, S., Takazawa, K. & Erneux, C. 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