T-cell-receptor signalling in inositol 1,4,5-trisphosphate receptor (IP3R) type-1-deficient mice:: is IP3R type 1 essential for T-cell-receptor signalling?
T-cell-receptor signalling in inositol 1,4,5-trisphosphate receptor (IP3R) type-1-deficient mice:: is IP3R type 1 essential for T-cell-receptor signalling?
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DOI：
10.1042/bj3330615
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发表时间：
1998-08-01
影响因子：
4.1
通讯作者：
Mikoshiba, K
中科院分区：
文献类型：
--
作者：
Hirota, J;Baba, M;Mikoshiba, K
Stimulation of T-cells via the T-cell receptor (TCR) complex is accompanied by an increase in intracellular Ca2+ concentration ([Ca2+](i)). Recently, it was reported that a stable transformant of the human T-cell line, Jurkat, expressing an antisense cDNA construct of inositol 1,4,5-trisphosphate receptor (IP3R) type 1 (IP(3)R1), failed to demonstrate increased [Ca2+](i) or interleukin-2 production after TCR stimulation and was also resistant to apoptotic stimuli. This cell line lacked IP(3)R1 expression, but expressed the type-2 and -3 receptors, IP(3)R2 and IP(3)R3 respectively [Jayaraman, Ondriasova, Ondrias, Harnick and Marks (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 6007-6011, and Jayaraman and Marks (1997) Mel. Cell. Biol. 17, 3005-3012]. The authors concluded that IP(3)R1 is essential for TCR signalling and suggested that Ca2+ release via IP(3)R1 is a critical mediator of apoptosis. To establish whether a loss of IP(3)R1 function in T-cells occurred in vivo and in vitro, we investigated Ca2+ signalling after TCR stimulation and the properties of T-cells using IP(3)R1-deficient (IP(3)R1-/-) mice. As IP(3)R1-/- mice die at weaning, we transplanted bone marrow cells of IP(3)R1-/- mice into irradiated wild-type mice. Western blot analysis showed that the recipient IP(3)R1-containing (IP(3)R1+/+) lymphocytes were replaced by the donor IP(3)R1-/- lymphocytes after transplantation and that expression of IP(3)R2 and IP(3)R3 was unaltered. In contrast with the previous reports, T-cells lacking IP(3)R1 were able to mobilize Ca2+ from intracellular Ca2+ stores after stimulation via the TCR. We observed no significant differences between IP(3)R1+/+ and IP(3)R1-/- T-cells in terms of the number of thymocytes and splenocytes, the proportion of the T-cell phenotype, proliferative response to anti-CD3 monoclonal antibody (mAb) stimulation and cell viability. Therefore IP(3)R1 is not essential for T-cell development and function.
