title: p70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I γ Degradation and Cell Invasion.
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.
authors: From the Markey Cancer Center and.|the Veterans Affairs Medical Center, Lexington, Kentucky 40502.
authors: Naser
authors: N
authors: Jafari
authors: From the Markey Cancer Center and.
authors: Qiaodan
authors: Q
authors: Zheng
authors: From the Markey Cancer Center and.
authors: Liqing
authors: L
authors: Li
authors: From the Markey Cancer Center and.
authors: Wei
authors: W
authors: Li
authors: From the Markey Cancer Center and.
authors: Lei
authors: L
authors: Qi
authors: From the Markey Cancer Center and.
authors: Jianyong
authors: J
authors: Xiao
authors: From the Markey Cancer Center and.
authors: Tianyan
authors: T
authors: Gao
authors: From the Markey Cancer Center and cai-huang@uky.edu.|the Veterans Affairs Medical Center, Lexington, Kentucky 40502.|the Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506 and.
authors: Cai
authors: http://orcid.org/0000-0003-4258-3841
authors: C
authors: Huang
mesh_terms: D000818:Animals; D016466:CHO Cells; D002465:Cell Movement / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C546842:MTOR protein, human; C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1
keywords: PIP5K1C; S6 kinase; cell invasion; cell migration; phosphatidylinositol kinase; protein degradation