PMID- 27780861
OWN - NLM
STAT- MEDLINE
DCOM- 20170526
LR  - 20220321
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 291
IP  - 49
DP  - 2016 Dec 2
TI  - p70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 
      4-Phosphate 5-Kinase Type I gamma Degradation and Cell Invasion.
PG  - 25729-25741
AB  - Phosphatidylinositol 4-phosphate 5-kinase type I gamma (PIPKIgamma90) ubiquitination and 
      subsequent degradation regulate focal adhesion assembly, cell migration, and 
      invasion. However, it is unknown how upstream signals control PIPKIgamma90 
      ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream 
      target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIgamma90 at 
      Thr-553 and Ser-555 and that S6K1-mediated PIPKIgamma90 phosphorylation is essential 
      for cell migration and invasion. Moreover, PIPKIgamma90 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 PIPKIgamma90 ubiquitination but enhanced the stability of PIPKIgamma90, and 
      depletion of S6K1 also enhanced the stability of PIPKIgamma90, indicating that 
      PIPKIgamma90 ubiquitination alone is insufficient for its degradation. These data 
      suggest that S6K1-mediated PIPKIgamma90 phosphorylation regulates cell migration and 
      invasion by controlling PIPKIgamma90 degradation.
CI  - (c) 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Jafari, Naser
AU  - Jafari N
AD  - From the Markey Cancer Center and.
AD  - the Veterans Affairs Medical Center, Lexington, Kentucky 40502.
FAU - Zheng, Qiaodan
AU  - Zheng Q
AD  - From the Markey Cancer Center and.
FAU - Li, Liqing
AU  - Li L
AD  - From the Markey Cancer Center and.
FAU - Li, Wei
AU  - Li W
AD  - From the Markey Cancer Center and.
FAU - Qi, Lei
AU  - Qi L
AD  - From the Markey Cancer Center and.
FAU - Xiao, Jianyong
AU  - Xiao J
AD  - From the Markey Cancer Center and.
FAU - Gao, Tianyan
AU  - Gao T
AD  - From the Markey Cancer Center and.
FAU - Huang, Cai
AU  - Huang C
AUID- ORCID: 0000-0003-4258-3841
AD  - From the Markey Cancer Center and cai-huang@uky.edu.
AD  - the Veterans Affairs Medical Center, Lexington, Kentucky 40502.
AD  - the Department of Pharmacology and Nutritional Sciences, University of Kentucky, 
      Lexington, Kentucky 40506 and.
LA  - eng
GR  - P30 CA177558/CA/NCI NIH HHS/United States
GR  - R01 CA133429/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20161025
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.68 (1-phosphatidylinositol-4-phosphate 5-kinase)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Cell Movement/*physiology
MH  - Cricetinae
MH  - Cricetulus
MH  - Focal Adhesions/genetics/*metabolism
MH  - Humans
MH  - Phosphorylation/physiology
MH  - Phosphotransferases (Alcohol Group Acceptor)/genetics/*metabolism
MH  - *Proteolysis
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics/*metabolism
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Ubiquitination/*physiology
PMC - PMC5207268
OTO - NOTNLM
OT  - PIP5K1C
OT  - S6 kinase
OT  - cell invasion
OT  - cell migration
OT  - phosphatidylinositol kinase
OT  - protein degradation
EDAT- 2016/10/27 06:00
MHDA- 2017/05/27 06:00
PMCR- 2017/12/02
CRDT- 2016/10/27 06:00
PHST- 2016/06/08 00:00 [received]
PHST- 2016/10/22 00:00 [revised]
PHST- 2016/10/27 06:00 [pubmed]
PHST- 2017/05/27 06:00 [medline]
PHST- 2016/10/27 06:00 [entrez]
PHST- 2017/12/02 00:00 [pmc-release]
AID - S0021-9258(20)34559-2 [pii]
AID - M116.742742 [pii]
AID - 10.1074/jbc.M116.742742 [doi]
PST - ppublish
SO  - J Biol Chem. 2016 Dec 2;291(49):25729-25741. doi: 10.1074/jbc.M116.742742. Epub 
      2016 Oct 25.