Cyclin-dependent kinase 1-mediated phosphorylation of protein kinase N1 promotes anchorage-independent growth and migration

Renya Zeng, Zhan Wang, Xinyue Li, Yuanhong Chen, Shuping Yang, Jixin Dong

Research output: Contribution to journalArticle

Abstract

Protein kinase N1 (PKN1) is a member of the protein kinase C superfamily. Aberrations of PKN1 kinase activity are involved in several human pathological processes, including cancer. We found that PKN family proteins (PKN1/2/3) are phosphorylated in response to antitubulin drug-induced mitotic arrest. We identified cyclin-dependent kinase 1 (CDK1) as the corresponding kinase for PKN protein phosphorylation. CDK1 phosphorylates PKN1 at S533, S537, S562, and S916 in vitro and in cells during drug-induced mitotic arrest. Immunofluorescence staining further confirmed that PKN1 phosphorylation occurs during normal mitosis in a CDK1-dependent manner. Knockdown of PKN1 significantly inhibited anchorage-independent growth and migration without affecting proliferation in multiple cancer cell lines. We further showed that mitotic phosphorylation is essential for PKN1's oncogenic function, as the non-phosphorylatable mutant PKN1-4A failed to rescue anchorage-independent growth and migration in PKN1-knockdown cells. Thus, our findings reveal a novel regulatory mechanism for PKN1 in mitosis and its role in tumorigenesis.

Original languageEnglish (US)
Article number109546
JournalCellular Signalling
Volume69
DOIs
StatePublished - May 2020

Keywords

  • CDK1
  • Mitotic phosphorylation
  • PKN1

ASJC Scopus subject areas

  • Cell Biology

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