Rac is involved in early TCR signaling
Rac is involved in early TCR signaling
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DOI：
10.4049/jimmunol.165.6.3182
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发表时间：
2000-09-15
影响因子：
4.4
通讯作者：
Trautmann, A
中科院分区：
文献类型：
--
作者：
Arrieumerlou, C;Randriamampita, C;Trautmann, A
GTTPac控制信号通路，通常与各种细胞类型中的肌动蛋白聚合相关。在T淋巴细胞中，Pac被Vav激活，Vav是与TCR相关的多蛋白转导复合物的主要组分。尽管在Vav缺陷小鼠中观察到了严重的信号传导缺陷，但尚未直接测试Pac在相应的早期TCR信号传导中的作用。在表达Rac的显性阴性（Rac N17）或组成型活性（Rac V12）形式的Jurkat T细胞中研究了这个问题。在表达Rac N17或Rac V12的T细胞中，抗CD 3诱导的Ca 2+应答和肌醇-1，4，5-三磷酸的产生被抑制。Pac突变体对Ca 2+信号传导的主要抑制作用施加在磷脂酶C-γ的活性上，并且在此之前，施加在ZAP-70和用于活化T细胞的连接分子LAT的磷酸化上。在对照细胞中观察到抗CD3诱导的肌动蛋白聚合的增加，但在用Pac突变体转染的细胞中未观察到。此外，latrunculin，结合到单体肌动蛋白，同时抑制基础和CD3诱导的肌动蛋白聚合和Ca2+信号，这些发现表明之间的联系所施加的影响Pac突变体对皮质肌动蛋白聚合和TCR信号。Pac在其GTP-和GDP-结合状态之间的循环对于这种信号传导是必要的。在早期TCR依赖性信号中观察到的改变表明Pac有助于TCR相关多蛋白转导复合物的组装。
The GTPase Pac controls signaling pathways often related to actin polymerization in various cell types. In T lymphocytes, Pac is activated by Vav, a major component of the multiprotein transduction complex associated to the TCR. Although profound signaling defects have been observed in Vav-deficient mice, a role of Pac in the corresponding early TCR signaling has not been tested directly. This question was investigated in Jurkat T cells transfected with either a dominant-negative (RacN17) or a constitutively active (RacV12) form of Rac, In T cells expressing either RacN17 or RacV12, the anti-CD3-induced Ca2+ response and production of inositol-1,4,5-trisphosphate were inhibited, The basal level of phosphatidylinositol-4,5-bisphosphate was not significantly diminished by Pac mutants. The major inhibitory effect of Pac mutants on Ca2+ signaling is exerted on the activity of phospholipase C-gamma and, before that, on the phosphorylation of ZAP-70 and of the linker molecule for activation of T cells, LAT, An anti-CD3-induced increase in actin polymerization was observed in control cells but not in cells transfected with a Pac mutant. In addition, latrunculin, which binds to monomeric actin, simultaneously inhibited basal and CD3-induced actin polymerization and Ca2+ signaling, These findings suggest a link between the effects exerted by Pac mutants on cortical actin polymerization and on TCR signaling. Pac cycling between its GTP- and GDP-bound states is necessary for this signaling. Alterations observed in early TCR-dependent signals suggest that Pac contributes to the assembly of the TCR-associated multiprotein transduction complex.