The cytoskeletal adaptor protein IQGAP1 regulates TCR-mediated signaling and filamentous actin dynamics.
The cytoskeletal adaptor protein IQGAP1 regulates TCR-mediated signaling and filamentous actin dynamics.
复制标题
DOI：
10.4049/jimmunol.1103487
复制
发表时间：
2012-06-15
期刊：
影响因子：
--
通讯作者：
Billadeau DD
中科院分区：
文献类型：
--
作者：
Gorman JA;Babich A;Dick CJ;Schoon RA;Koenig A;Gomez TS;Burkhardt JK;Billadeau DD
Ras gtpase激活样蛋白IQGAP1是一种多模块支架，控制成纤维细胞和上皮细胞的信号传导和细胞骨架调节。然而，IQGAP1在T细胞发育、激活和细胞骨架调节中的功能作用尚未被研究。本研究表明，在CD8+ T细胞中，IQGAP1在胸腺细胞发育、微管组织中心极化和细胞溶解功能中都是不可或缺的。然而，IQGAP1缺失的CD8+ T细胞，以及IQGAP1抑制的Jurkat T细胞反应过度，表现出IL-2和IFN-γ产生增加，LCK激活增加，TCR连接后全球磷酸化动力学增强。此外，iqgap1缺陷T细胞在扩散过程中表现出tcr介导的f -肌动蛋白组装增加和f -肌动蛋白速度加快。此外，我们发现IQGAP1的离散区域调节细胞活化和f -肌动蛋白积累。综上所述，我们的数据表明IQGAP1在T细胞中作为双重负调节因子，通过不同的机制限制tcr介导的激活动力学和f -肌动蛋白动力学。
The Ras GTPase-activating-like protein IQGAP1 is a multi-modular scaffold that controls signaling and cytoskeletal regulation in fibroblasts and epithelial cells. However, the functional role of IQGAP1 in T cell development, activation and cytoskeletal regulation has not been investigated. Herein, we show that IQGAP1 is dispensable for thymocyte development, as well as microtubule organizing center polarization and cytolytic function in CD8+ T cells. However, IQGAP1-deficient CD8+ T cells, as well as Jurkat T cells suppressed for IQGAP1 were hyper-responsive, displaying increased IL-2 and IFN-γ production, heightened LCK activation, and augmented global phosphorylation kinetics following TCR ligation. Additionally, IQGAP1-deficient T cells exhibited increased TCR-mediated F-actin assembly and amplified F-actin velocities during spreading. Moreover, we found that discrete regions of IQGAP1 regulated cellular activation and F-actin accumulation. Taken together, our data suggest that IQGAP1 acts as a dual negative regulator in T cells, limiting both TCR-mediated activation kinetics and F-actin dynamics via distinct mechanisms.
登录
查看更多内容
影响因子：
64.5
作者：
Drees, F;Pokutta, S;Weis, WI
通讯作者：
Weis, WI
影响因子：
64.5
作者：
Fukata, M;Watanabe, T;Kaibuchi, K
通讯作者：
Kaibuchi, K
DIA1和IQGAP1在细胞迁移和吞噬杯形成中相互作用。
影响因子：
7.8
作者：
Brandt, Dominique T.;Marion, Sabrina;Griffiths, Gareth;Watanabe, Takashi;Kaibuchi, Kozo;Grosse, Robert
通讯作者：
Grosse, Robert
影响因子：
9.2
作者：
Holsinger, LJ;Graef, IA;Crabtree, GR
通讯作者：
Crabtree, GR
影响因子：
4.4
作者：
Gil, Diana;Schrum, Adam G.;Palmer, Ed
通讯作者：
Palmer, Ed