E‐Cadherin Facilitates Protein Kinase D1 Activation and Subcellular Localization. Issue 12 (1st April 2016)

• Record Type: Journal Article
• Authors: Li, Zhuo; Zhang, Chuanyou; Chen, Li; Li, Guosheng; Qu, Ling; Balaji, K.C.; Du, Cheng
• Is Part Of: Journal of cellular physiology. Volume 231:Issue 12(2016:Dec.)
• Page Start: 2741
• Page End: 2748
• Publication Date: 2016-04-01
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.25382
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : 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. J. Cell. Physiol. 231: 2741–2748, 2016. © 2016 Wiley Periodicals, Inc. Abstract : E‐cadherin intracellular domain directly binds to PKD1 C1 domain. This interesction regulates PKD1 subcellular localization and activation.