PMID- 20410302
OWN - NLM
STAT- MEDLINE
DCOM- 20100721
LR  - 20211203
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 285
IP  - 25
DP  - 2010 Jun 18
TI  - Mammalian target of rapamycin (mTOR) and S6 kinase down-regulate phospholipase D2 
      basal expression and function.
PG  - 18991-9001
LID - 10.1074/jbc.M110.111542 [doi]
AB  - The mammalian target of rapamycin (mTOR) and S6 kinase (S6K) pathway is essential 
      for cell differentiation, growth, and survival. Phospholipase D2 (PLD2) plays a 
      key role in mTOR/S6K mitogenic signaling. However, the impact of PLD on mTOR/S6K 
      gene expression is not known. Here we show that interleukin-8 (IL-8) increases 
      mRNA expression levels for PLD2, mTOR, and S6K, with PLD2 preceding mTOR/S6K in 
      time. Silencing of PLD2 gene expression abrogated IL-8-induced mTOR/S6K mRNA 
      expression, whereas silencing of mTOR or S6K gene expression resulted in large 
      (>3-fold and >5-fold, respectively) increased levels of PLD2 RNA, which was 
      paralleled by increases in protein expression and lipase activity. Treatment of 
      cells with 0.5 nm rapamycin induced a similar trend. These results suggest that, 
      under basal conditions, PLD2 expression and concomitant activity is negatively 
      regulated by the mTOR/S6K signaling pathway. Down-regulation of PLD2 was 
      confirmed in differentiated HL-60 leukocytes overexpressing an mTOR-wild type, 
      but not an mTOR kinase-dead construct. At the cellular level, overexpression of 
      mTOR-wild type resulted in lower basal cell migration, which was reversed by 
      treatment with IL-8. We propose that IL-8 reverses an mTOR/S6K-led 
      down-regulation of PLD2 expression and enables PLD2 to fully function as a 
      facilitator for cell migration.
FAU - Tabatabaian, Farnaz
AU  - Tabatabaian F
AD  - Department of Biochemistry and Molecular Biology, Wright State University School 
      of Medicine, Dayton, Ohio 45435, USA.
FAU - Dougherty, Kevin
AU  - Dougherty K
FAU - Di Fulvio, Mauricio
AU  - Di Fulvio M
FAU - Gomez-Cambronero, Julian
AU  - Gomez-Cambronero J
LA  - eng
GR  - R01 HL056653/HL/NHLBI NIH HHS/United States
GR  - R29 HL056653/HL/NHLBI NIH HHS/United States
GR  - HL056653/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100421
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Interleukin-8)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.1.3 (Lipase)
RN  - EC 3.1.4.- (phospholipase D2)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Cell Differentiation
MH  - Chlorocebus aethiops
MH  - *Gene Expression Regulation, Enzymologic
MH  - Gene Silencing
MH  - HL-60 Cells
MH  - Humans
MH  - Interleukin-8/metabolism
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Lipase/metabolism
MH  - Neutrophils/metabolism
MH  - Phospholipase D/*biosynthesis
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Ribosomal Protein S6 Kinases/*biosynthesis
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
PMC - PMC2885176
EDAT- 2010/04/23 06:00
MHDA- 2010/07/22 06:00
PMCR- 2011/06/18
CRDT- 2010/04/23 06:00
PHST- 2010/04/23 06:00 [entrez]
PHST- 2010/04/23 06:00 [pubmed]
PHST- 2010/07/22 06:00 [medline]
PHST- 2011/06/18 00:00 [pmc-release]
AID - S0021-9258(20)58029-0 [pii]
AID - M110.111542 [pii]
AID - 10.1074/jbc.M110.111542 [doi]
PST - ppublish
SO  - J Biol Chem. 2010 Jun 18;285(25):18991-9001. doi: 10.1074/jbc.M110.111542. Epub 
      2010 Apr 21.