Roles of p-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod formation.

Roles of p-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod formation.
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Perm和Rho-Rock信号传导在淋巴细胞极性和uropod形成中的作用。

DOI:
10.1083/jcb.200403091
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发表时间:
2004-10-25
影响因子:
7.8
通讯作者:
Shimizu, A
Shimizu, A
中科院分区:
生物学1区
文献类型:
--
作者:
Lee, JH;Katakai, T;Hara, T;Gonda, H;Sugai, M;Shimizu, A

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运动细胞前后不对称对有效的定向运动至关重要。移行淋巴细胞的尾足是一个后部突起,其中集中了几种蛋白质,包括CD44和ezrin/radixin/moesin (ERM)。EL4。在G8 t淋巴瘤细胞中,ezrin cooh末端Thr567磷酸化调控ezrin在尾足动物中的选择性定位。过表达类似磷酸化的T567D ezrin可以增强尾足的大小和细胞迁移。T567D ezrin还诱导cd44相关的极帽的构建,该极帽覆盖在staurosporine处理的尾足类破坏的EL4细胞的后细胞质上。G8细胞或自然未极化的X63.653骨髓瘤细胞以肌动蛋白细胞骨架依赖的方式。rho相关的含卷曲卷曲蛋白激酶(ROCK)抑制剂Y-27632破坏尾足,但不破坏极帽,表明Rho-ROCK信号是后突所必需的,而不是ERM磷酸化所必需的。磷酸化ezrin通过其nh2末端结构域与Dbl结合并引起Rho活化。此外,本构活性的Q63L RhoA选择性地定位于细胞后部。因此,磷酸化的ERM在T淋巴细胞中诱导尾足的质膜“后发性”中具有潜在的功能。
Front–rear asymmetry in motile cells is crucial for efficient directional movement. The uropod in migrating lymphocytes is a posterior protrusion in which several proteins, including CD44 and ezrin/radixin/moesin (ERM), are concentrated. In EL4.G8 T-lymphoma cells, Thr567 phosphorylation in the COOH-terminal domain of ezrin regulates the selective localization of ezrin in the uropod. Overexpression of the phosphorylation-mimetic T567D ezrin enhances uropod size and cell migration. T567D ezrin also induces construction of the CD44-associated polar cap, which covers the posterior cytoplasm in staurosporine-treated, uropod-disrupted EL4.G8 cells or in naturally unpolarized X63.653 myeloma cells in an actin cytoskeleton–dependent manner. Rho-associated coiled coil–containing protein kinase (ROCK) inhibitor Y-27632 disrupts the uropod but not the polar cap, indicating that Rho–ROCK signaling is required for posterior protrusion but not for ERM phosphorylation. Phosphorylated ezrin associates with Dbl through its NH2-terminal domain and causes Rho activation. Moreover, constitutively active Q63L RhoA is selectively localized in the rear part of the cells. Thus, phosphorylated ERM has a potential function in establishing plasma membrane “posteriority” in the induction of the uropod in T lymphocytes.
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