E-钙黏蛋白脱离会激活Rap1 GTP酶。
E-cadherin dis-engagement activates the Rap1 GTPase.
作者信息
Asuri Sirisha, Yan Jingliang, Paranavitana Nivanka C, Quilliam Lawrence A
机构信息
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and Walther Oncology Center, Indianapolis, Indiana 46202, USA.
出版信息
J Cell Biochem. 2008 Nov 1;105(4):1027-37. doi: 10.1002/jcb.21902.
Abstract
E-cadherin based adherens junctions are finely regulated by multiple cellular signaling events. Here we show that the Ras-related Rap1 GTPase is enriched in regions of nascent cell-cell contacts and strengthens E-cadherin junctions: constitutively active Rap1 expressing MDCK cells exhibit increased junctional contact and resisted calcium depletion-induced cell-cell junction disruption. E-cadherin disengagement activated Rap1 and this correlated with E-cadherin association with the Rap GEFs, C3G and PDZ-GEF I. PDZ-GEF I associated with E-cadherin and beta-catenin whereas C3G interaction with E-cadherin did not involve beta-catenin. Knockdown of PDZ-GEF I in MDCK cells decreased Rap1 activity following E-cadherin junction disruption. We hereby show that Rap1 plays a role in the maintenance and repair of E-cadherin junctions and is activated via an "outside-in" signaling pathway initiated by E-cadherin and mediated at least in part by PDZ-GEF I.
摘要
基于E-钙黏蛋白的黏着连接受到多种细胞信号事件的精细调控。在此我们表明，与Ras相关的Rap1 GTP酶在新生细胞间接触区域富集，并增强E-钙黏蛋白连接：持续表达活性Rap1的MDCK细胞表现出增加的连接接触，并抵抗钙耗竭诱导的细胞间连接破坏。E-钙黏蛋白脱离激活Rap1，这与E-钙黏蛋白与Rap鸟苷酸交换因子C3G和PDZ-GEF I的结合相关。PDZ-GEF I与E-钙黏蛋白和β-连环蛋白相关，而C3G与E-钙黏蛋白的相互作用不涉及β-连环蛋白。在MDCK细胞中敲低PDZ-GEF I会降低E-钙黏蛋白连接破坏后的Rap1活性。我们在此表明，Rap1在E-钙黏蛋白连接的维持和修复中起作用，并通过由E-钙黏蛋白启动且至少部分由PDZ-GEF I介导的“由外向内”信号通路被激活。
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