E-Cadherin Facilitates Protein Kinase D1 Activation and Subcellular Localization

Li Zhuo; Zhang Chuanyou; Chen LiLi GuoshengQu LingBalaji K. C.Du Cheng

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E-Cadherin Facilitates Protein Kinase D1 Activation and Subcellular Localization

机译：钙粘蛋白促进蛋白激酶D1激活和亚细胞定位

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Protein kinase D 1 (PKD1) is a serine/threonine kinase implicated in the regulation of diverse cellular functions including cell growth, differentiation, adhesion and motility. The current model for PKD1 activation involves diacylglycerol (DAG) binding to the C1 domain of PKD1 which results in the translocation of PKD1 to subcellular membranes where PKD1 is phosphorylated and activated by protein kinase C (PKC). In this study, we have identified a novel regulation of PKD1 activation. The epithelial cell membrane protein E-cadherin physically binds to PKD1 which leads to a subcellular redistribution of PKD1. Furthermore, artificial targeting of PKD1 to the membrane leads to PKD1 activation in a PKC-independent manner, indicating that membrane attachment is sufficient enough to activate PKD1. The presence of E-cadherin dynamically regulates PKD1 activation by Bryostatin 1, a potent activator of PKD1, and its substrate phosphorylation specificity, implying a loss of E-cadherin during cancer metastasis could cause the re-distribution PKD1 and re-wiring of PKD1 signaling for distinct functions. The knocking down of PKD1 in lung epithelial cell line A549 results in an epithelial to mesenchymal transition with changes in biomarker expression, cell migration and drug resistance. These results extend our previous understanding of PKD1 regulation and E-cadherin signaling functions and may help to explain the diversified functions of PKD1 in various cells. (C) 2016 Wiley Periodicals, Inc.

机译：蛋白激酶1 D (PKD1)是一种丝氨酸/苏氨酸激酶参与多元化的监管细胞功能,包括细胞生长分化、附着力和能动性。当前模型PKD1激活涉及甘油二酯(DAG)绑定的C1域PKD1 PKD1易位的结果亚细胞的膜PKD1在哪里磷酸化,激活蛋白激酶C(PKC)。监管PKD1激活。细胞膜蛋白质钙粘蛋白结合PKD1导致亚细胞PKD1的再分配。针对膜导致PKD1 PKD1的激活PKC-independent的方式,表明膜附件是充分的足以激活PKD1。钙粘蛋白动态调节PKD1激活苔藓虫素1,PKD1的有力催化剂它的底物磷酸化特异性,暗示粘附在癌症的丧失PKD1转移可能导致的再分配和听觉PKD1信号明显功能。上皮细胞系A549的结果上皮间质转型与变化在生物标志物表达,细胞迁移和药物阻力。理解PKD1监管和钙粘蛋白信号功能和可能有助于解释多样化的功能PKD1在各种细胞。(C) 2016年威利期刊公司。

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来源
《Journal of Cellular Physiology》 |2016年第12期|2741-2748|共8页
作者
Li Zhuo; Zhang Chuanyou; Chen LiLi GuoshengQu LingBalaji K. C.Du Cheng;
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作者单位

Wake Forest Univ, Dept Urol, Winston Salem, NC 27109 USA;

China Med Univ, Affiliated Hosp 1, Shenyang, Peoples R China;

Shandong Acad Agr Sci, Jinan, Peoples R ChinaUniv Massachusetts, Sch Med, Dept Surg, 364 Plantat St, Worcester, MA 01605 USA;

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正文语种英语
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关键词
PKD1 gene; Cdh1 Proteins; DAG/PE-Binding Domain;

机译：PKD1基因,蛋白质是携带者;DAG / PE-Binding域;

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E-Cadherin Facilitates Protein Kinase D1 Activation and Subcellular Localization

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