PMID- 32605013
OWN - NLM
STAT- MEDLINE
DCOM- 20210412
LR  - 20240303
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 9
IP  - 7
DP  - 2020 Jun 27
TI  - mTORC2 Is Involved in the Induction of RSK Phosphorylation by Serum or Nutrient 
      Starvation.
LID - 10.3390/cells9071567 [doi]
LID - 1567
AB  - Cells adjust to nutrient fluctuations to restore metabolic homeostasis. The 
      mechanistic target of rapamycin (mTOR) complex 2 responds to nutrient levels and 
      growth signals to phosphorylate protein kinases belonging to the AGC (Protein 
      Kinases A,G,C) family such as Akt and PKC. Phosphorylation of these AGC kinases 
      at their conserved hydrophobic motif (HM) site by mTORC2 enhances their 
      activation and mediates the functions of mTORC2 in cell growth and metabolism. 
      Another AGC kinase family member that is known to undergo increased 
      phosphorylation at the homologous HM site (Ser380) is the p90 ribosomal S6 kinase 
      (RSK). Phosphorylation at Ser380 is facilitated by the activation of the 
      mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) 
      in response to growth factor stimulation. Here, we demonstrate that optimal 
      phosphorylation of RSK at this site requires an intact mTORC2. We also found that 
      RSK is robustly phosphorylated at Ser380 upon nutrient withdrawal or inhibition 
      of glycolysis, conditions that increase mTORC2 activation. However, 
      pharmacological inhibition of mTOR did not abolish RSK phosphorylation at Ser380, 
      indicating that mTOR catalytic activity is not required for this phosphorylation. 
      Since RSK and SIN1beta colocalize at the membrane during serum restimulation and 
      acute glutamine withdrawal, mTORC2 could act as a scaffold to enhance RSK HM site 
      phosphorylation. Among the known RSK substrates, the CCTbeta subunit of the 
      chaperonin containing TCP-1 (CCT) complex had defective phosphorylation in the 
      absence of mTORC2. Our findings indicate that the mTORC2-mediated phosphorylation 
      of the RSK HM site could confer RSK substrate specificity and reveal that RSK 
      responds to nutrient fluctuations.
FAU - Chou, Po-Chien
AU  - Chou PC
AD  - Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson 
      Medical School, Piscataway, NJ 08854, USA.
FAU - Rajput, Swati
AU  - Rajput S
AUID- ORCID: 0000-0001-8794-4300
AD  - Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson 
      Medical School, Piscataway, NJ 08854, USA.
FAU - Zhao, Xiaoyun
AU  - Zhao X
AD  - Department of Immunology and Microbiology, Shanghai Jiao Tong University School 
      of Medicine, Shanghai 200240, China.
FAU - Patel, Chadni
AU  - Patel C
AD  - Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson 
      Medical School, Piscataway, NJ 08854, USA.
FAU - Albaciete, Danielle
AU  - Albaciete D
AD  - Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson 
      Medical School, Piscataway, NJ 08854, USA.
FAU - Oh, Won Jun
AU  - Oh WJ
AD  - Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson 
      Medical School, Piscataway, NJ 08854, USA.
FAU - Daguplo, Heineken Queen
AU  - Daguplo HQ
AUID- ORCID: 0000-0002-3669-1144
AD  - Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson 
      Medical School, Piscataway, NJ 08854, USA.
FAU - Patel, Nikhil
AU  - Patel N
AD  - Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson 
      Medical School, Piscataway, NJ 08854, USA.
FAU - Su, Bing
AU  - Su B
AD  - Department of Immunology and Microbiology, Shanghai Jiao Tong University School 
      of Medicine, Shanghai 200240, China.
FAU - Werlen, Guy
AU  - Werlen G
AD  - Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson 
      Medical School, Piscataway, NJ 08854, USA.
FAU - Jacinto, Estela
AU  - Jacinto E
AUID- ORCID: 0000-0001-7118-1759
AD  - Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson 
      Medical School, Piscataway, NJ 08854, USA.
LA  - eng
GR  - P41 RR012408/RR/NCRR NIH HHS/United States
GR  - R01 GM137493/GM/NIGMS NIH HHS/United States
GR  - T32 GM135141/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200627
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Carrier Proteins)
RN  - 0 (stress-activated protein kinase-interacting protein, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
RN  - EC 3.6.1.- (Chaperonins)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/genetics/metabolism
MH  - Cell Membrane/metabolism
MH  - Chaperonins/genetics/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Mechanistic Target of Rapamycin Complex 2/genetics/*metabolism
MH  - Mice
MH  - Phosphorylation
MH  - Ribosomal Protein S6 Kinases, 90-kDa/genetics/metabolism
MH  - Thymocytes/*metabolism
PMC - PMC7408474
OTO - NOTNLM
OT  - AGC kinases
OT  - CCT/TRiC
OT  - CCTbeta
OT  - MAPK/ERK
OT  - RSK
OT  - chaperonin
OT  - mTORC2
OT  - metabolism
OT  - nutrients
OT  - p90 ribosomal s6 kinase
OT  - starvation
COIS- The authors declare no competing interests.
EDAT- 2020/07/02 06:00
MHDA- 2021/04/13 06:00
PMCR- 2020/07/01
CRDT- 2020/07/02 06:00
PHST- 2020/05/03 00:00 [received]
PHST- 2020/06/17 00:00 [revised]
PHST- 2020/06/23 00:00 [accepted]
PHST- 2020/07/02 06:00 [entrez]
PHST- 2020/07/02 06:00 [pubmed]
PHST- 2021/04/13 06:00 [medline]
PHST- 2020/07/01 00:00 [pmc-release]
AID - cells9071567 [pii]
AID - cells-09-01567 [pii]
AID - 10.3390/cells9071567 [doi]
PST - epublish
SO  - Cells. 2020 Jun 27;9(7):1567. doi: 10.3390/cells9071567.