Directional sensing requires Gβγ-mediated PAK1 and PIXα-dependent activation of cdc42
Directional sensing requires Gβγ-mediated PAK1 and PIXα-dependent activation of cdc42
复制标题
DOI：
10.1016/s0092-8674(03)00559-2
复制
发表时间：
2003-07-25
期刊：
影响因子：
64.5
通讯作者：
Wu, DQ
中科院分区：
文献类型：
--
作者：
Li, Z;Hannigan, M;Wu, DQ
有效的趋化性需要定向感应和细胞极化。我们描述了一个信号机制，涉及G β γ，PAK相关的鸟嘌呤核苷酸交换因子（PIXalpha），Cdc 42，和p21激活激酶（PAK）1。该途径被化学引诱物利用来调节髓样细胞的定向感知和定向迁移。我们的研究结果表明，Gbetagamma结合PAKI，并通过PAK相关的PIXa激活Cdc 42，进而激活PAK 1。因此，在该途径中，PAKII不仅是Cdc 42的效应物，而且还作为Cdc 42活化所需的支架蛋白发挥作用。该Gbetagamma-PAK 1/PIXalpha/Cdc 42通路对于将F-肌动蛋白形成定位于前沿、将PTEN从前沿排除、定向传感和趋化性白细胞的持续定向迁移是必不可少的。虽然配体诱导的PIP 3的产生不是该途径激活所必需的，但PIP 3似乎通过该途径定位Cdc 42的激活。
Efficient chemotaxis requires directional sensing and cell polarization. We describe a signaling mechanism involving Gbetagamma, PAK-associated guanine nucleotide exchange factor (PIXalpha), Cdc42, and p21-activated kinase (PAK) 1. This pathway is utilized by chemoattractants to regulate directional sensing and directional migration of myeloid cells. Our results suggest that Gbetagamma binds PAKI and, via PAK-associated PIXa, activates Cdc42, which in turn activates PAK1. Thus, in this pathway, PAKII is not only an effector for Cdc42, but it also functions as a scaffold protein required for Cdc42 activation. This Gbetagamma-PAK1/PIXalpha/Cdc42 pathway is essential for the localization of F-actin formation to the leading edge, the exclusion of PTEN from the leading edge, directional sensing, and the persistent directional migration of chemotactic leukocytes. Although ligand-induced production Of PIP3 is not required for activation of this pathway, PIP3 appears to localize the activation of Cdc42 by the pathway.