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

Phosphatidylinositol 4-phosphate 5-kinase type I (PIPKI90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKI90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKI90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKI90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKI90 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 PIPKI90 ubiquitination but enhanced the stability of PIPKI90, and depletion of S6K1 also enhanced the stability of PIPKI90, indicating that PIPKI90 ubiquitination alone is insufficient for its degradation. These data suggest that S6K1-mediated PIPKI90 phosphorylation regulates cell migration and invasion by controlling PIPKI90 degradation.