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Inositol (1,4,5) trisphosphate 3 kinase B controls positive selection of T cells and modulates Erk activity.

Wen, Ben, Pletcher, Mathew, Warashina, Masaki, Choe, Sun Hui, Ziaee, Niusha, Wiltshire, Timothy, Sauer, Karsten and Cooke, Michael (2004) Inositol (1,4,5) trisphosphate 3 kinase B controls positive selection of T cells and modulates Erk activity. Proceedings of the National Academy of Sciences of the United States of America, 101 (15). pp. 5604-5609. ISSN 0027-8424


The mechanisms governing positive selection of T cells in the thymus are still incompletely understood. Here, we describe a N-ethyl-N-nitrosourea induced recessive mouse mutant, Ms. T-less, which lacks T cells in the peripheral blood because of a complete block of thymocyte development at the CD4(+)CD8(+) stage. Single nucleotide polymorphism mapping and candidate gene sequencing revealed a nonsense mutation in the inositol (1,4,5) trisphosphate 3 kinase B (Itpkb) gene in Ms. T-less mice. Accordingly, Ms. T-less 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(2+) signaling. Surprisingly, Ca(2+) 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 Ms. T-less thymocytes, suggesting a role for Itpkb in linking T cell receptor signaling to efficient and sustained Erk activation.

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Additional Information: free final full text version available at publisher's official URL and at PubMedCentral; author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
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Date Deposited: 14 Dec 2009 14:02
Last Modified: 31 Jan 2013 01:21


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