E-cadherin phosphorylation by protein kinase D1/protein kinase Cμ is associated with altered cellular aggregation and motility in prostate cancer

Meena Jaggi, Prema S. Rao, David J. Smith, Margaret J. Wheelock, Keith R Johnson, George P. Hemstreet, K. C. Balaji

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

The cadherin family of transmembrane glycoproteins plays a critical role in cell-to-cell adhesion and cadherin dysregulation is strongly associated with cancer metastasis and progression. In this study, we report a novel interaction between protein kinase D1 [PKD1; formerly known as protein kinase C μ (PKCμ)] and E-cadherin. PKD1 is a serine/threonine-specific kinase known to play a role in multiple cellular processes including apoptosis, cytoskeleton remodeling, and invasion. Our study shows that PKD1 colocalizes with E-cadherin at cell junctions in LNCaP prostate cancer cells and coimmunoprecipitates with E-cadherin from lysates of LNCaP cells. In vitro kinase assays have shown that PKD1 phosphorylates E-cadherin. Inhibition of PKD1 activity by the selective inhibitor Gö6976 in LNCaP cells resulted in decreased cellular aggregation and overexpression of PKD1 in C4-2 prostate cancer cells increased cellular aggregation and decreased cellular motility. We also validated the PKD1 and E-cadherin colocalization in human prostate cancer tissue by confocal laser scanning microscopy. Our study has identified E-cadherin as a novel substrate of PKD1, and phosphorylation of E-cadherin by PKD1 is associated with increased cellular aggregation and decreased cellular motility in prostate cancer. Because both E-cadherin and PKD1 are known to be dysregulated in prostate cancer, our study identified an important protein-protein interaction influencing the signal transduction system associated with cell adhesion in prostate cancer.

Original languageEnglish (US)
Pages (from-to)483-492
Number of pages10
JournalCancer Research
Volume65
Issue number2
Publication statusPublished - Jan 15 2005

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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