p70S6K1 (S6K1)-Mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I γ Degradation and Cell Invasion

Authors

Naser Jafari, University of KentuckyFollow
Qiaodan Zheng, University of Kentucky
Liqing Li, University of KentuckyFollow
Wei Li, University of Kentucky
Lei Qi, University of KentuckyFollow
Jianyong Xiao, University of Kentucky
Tianyan Gao, University of KentuckyFollow
Cai Huang, University of KentuckyFollow

Abstract

Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKIγ90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKIγ90 phosphorylation is required for the development of focal adhesions and invadopodia, key machineries for cell migration and invasion. Surprisingly, substitution of Thr-553 and Ser-555 with Ala promoted PIPKIγ90 ubiquitination but enhanced the stability of PIPKIγ90, and depletion of S6K1 also enhanced the stability of PIPKIγ90, indicating that PIPKIγ90 ubiquitination alone is insufficient for its degradation. These data suggest that S6K1-mediated PIPKIγ90 phosphorylation regulates cell migration and invasion by controlling PIPKIγ90 degradation.

Document Type

Article

Publication Date

10-25-2016

Notes/Citation Information

Published in Journal of Biological Chemistry, v. 291, no. 49, p. 25729-25741.

This research was originally published in the Journal of Biological Chemistry. Jafari, N., Zheng, Q., Li, L., Li, W., Qi, L., Xiao, J., Gao, T., and Huang, C. p70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I γ Degradation and Cell Invasion. J. Biol. Chem. 2016; 291: 25729-25741. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The copyright holder has granted the permission for posting the article here.

Digital Object Identifier (DOI)

https://doi.org/10.1074/jbc.M116.742742

Funding Information

This work was supported by American Cancer Society Research Scholar Grant RSG-13-184-01-CSM (to C. H.).

Related Content

This article contains supplemental Figs. S1–S3.

Repository Citation

Jafari, Naser; Zheng, Qiaodan; Li, Liqing; Li, Wei; Qi, Lei; Xiao, Jianyong; Gao, Tianyan; and Huang, Cai, "p70S6K1 (S6K1)-Mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I γ Degradation and Cell Invasion" (2016). Markey Cancer Center Faculty Publications. 79.
https://uknowledge.uky.edu/markey_facpub/79