Cdk5-mediated phosphorylation regulates phosphatidylinositol 4-phosphate 5-kinase type i γ90 activity and cell invasion

Liqing Li, Tomasz Kolodziej, Naser Jafari, Jing Chen, Haining Zhu, Zenon Rajfur, Cai Huang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Phosphatidylinositol 4-phosphate 5-kinase type I g (PIPKIγ90) regulates cell migration, invasion, and metastasis. However, it is unknown how cellular signals regulate those processes. Here, we show that cyclindependent kinase 5 (Cdk5), a protein kinase that regulates cell migration and invasion, phosphorylates PIPKIγ90 at S453, and that Cdk5-mediated PIPKIγ90 phosphorylation is essential for cell invasion. Moreover, Cdk5-mediated phosphorylation down-regulates the activity of PIPKIγ90 and the secretion of fibronectin, an extracellular matrix protein that regulates cell migration and invasion. Furthermore, inhibition of PIPKIg activity with the chemical inhibitor UNC3230 suppresses fibronectin secretion in a dose-dependent manner, whereas depletion of Cdk5 enhances fibronectin secretion. With total internal reflection fluorescence microscopy, we found that secreted fibronectin appears as round dots, which colocalize with Tks5 and CD9 but not with Zyxin. These data suggest that Cdk5-mediated PIPKIγ90 phosphorylation regulates cell invasion by controlling PIPKIγ90 activity and fibronectin secretion.

Original languageEnglish
Pages (from-to)631-642
Number of pages12
JournalFASEB Journal
Issue number1
StatePublished - Jan 2019

Bibliographical note

Funding Information:
This work was supported by American Cancer Society Research Scholar Grant RSG-13-184-01CSM (to C.H.) and U.S. National Institutes of Health, National Institute of General Medical Sciences Grant R01 GM122994 (to C.H.). The authors declare no conflicts of interest.

Publisher Copyright:


  • Cell migration
  • Extracellular matrix protein
  • Fibronectin
  • Phosphatidylinositol kinase
  • Secretion

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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