Cdk5-mediated phosphorylation regulates phosphatidylinositol 4-phosphate 5-kinase type I ? 90 activity and cell invasion.

ABSTRACT: Phosphatidylinositol 4-phosphate 5-kinase type I ? (PIPKI?90) regulates cell migration, invasion, and metastasis. However, it is unknown how cellular signals regulate those processes. Here, we show that cyclin-dependent kinase 5 (Cdk5), a protein kinase that regulates cell migration and invasion, phosphorylates PIPKI?90 at S453, and that Cdk5-mediated PIPKI?90 phosphorylation is essential for cell invasion. Moreover, Cdk5-mediated phosphorylation down-regulates the activity of PIPKI?90 and the secretion of fibronectin, an extracellular matrix protein that regulates cell migration and invasion. Furthermore, inhibition of PIPKI? 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 PIPKI?90 phosphorylation regulates cell invasion by controlling PIPKI?90 activity and fibronectin secretion.-Li, L., Ko?odziej, T., Jafari, N., Chen, J., Zhu, H., Rajfur, Z., Huang, C. Cdk5-mediated phosphorylation regulates phosphatidylinositol 4-phosphate 5-kinase type I ? 90 activity and cell invasion.

SUBMITTER: Li L 

PROVIDER: S-EPMC6355064 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature