PMID- 16837165
OWN - NLM
STAT- MEDLINE
DCOM- 20070205
LR  - 20211203
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 18
IP  - 12
DP  - 2006 Dec
TI  - PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals.
PG  - 2283-91
AB  - Mammalian target-of-rapamycin (mTOR), which is a master controller of cell 
      growth, senses a mitogenic signal in part through the lipid second messenger 
      phosphatidic acid (PA), generated by phospholipase D (PLD). To understand further 
      which isozymes of PLD are involved in this process, we compared the effect of PLD 
      isozymes on mTOR activation. We found that PLD2 has an essential role in 
      mitogen-induced mTOR activation as the siRNA-mediated knockdown of PLD2, not of 
      PLD1, profoundly reduced the phosphorylations of S6K1 and 4EBP1, well-known mTOR 
      effectors. Furthermore, exogenous PA-induced mTOR activation was abrogated by 
      PLD2 knockdown, but not by PLD1 knockdown. This abrogation was found to be the 
      result of complex formation between PLD2 and mTOR/raptor. PLD2 possesses a 
      TOS-like motif (Phe-Glu-Val-Gln-Val, a.a. 265-269), through which it interacts 
      with raptor independently of the other TOS motif-containing proteins, S6K1 and 
      4EBP1. PLD2-dependent mTOR activation appears to require PLD2 binding to 
      mTOR/raptor with lipase activity, since lipase-inactive PLD2 cannot trigger mTOR 
      activation despite its ability to interact with mTOR/raptor. Abrogation of 
      mitogen-dependent mTOR activation by PLD2 knockdown was rescued only by wild type 
      PLD2, but not by raptor binding-deficient and lipase-inactive PLD2. Our results 
      demonstrate the importance of localized PA generation for the mitogen-induced 
      activation of mTOR, which is achieved by a specific interaction between PLD2 and 
      mTOR/raptor.
FAU - Ha, Sang Hoon
AU  - Ha SH
AD  - Division of Molecular and Life Sciences, Pohang University of Science and 
      Technology, Pohang, Kyungbook 790-784, Republic of Korea.
FAU - Kim, Do-Hyung
AU  - Kim DH
FAU - Kim, Il-Shin
AU  - Kim IS
FAU - Kim, Jung Hwan
AU  - Kim JH
FAU - Lee, Mi Nam
AU  - Lee MN
FAU - Lee, Hyun Ju
AU  - Lee HJ
FAU - Kim, Jong Heon
AU  - Kim JH
FAU - Jang, Sung Key
AU  - Jang SK
FAU - Suh, Pann-Ghill
AU  - Suh PG
FAU - Ryu, Sung Ho
AU  - Ryu SH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060603
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Mitogens)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.4.- (phospholipase D2)
RN  - EC 3.1.4.4 (Phospholipase D)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites/genetics
MH  - Blotting, Western
MH  - COS Cells
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - Genetic Vectors/genetics
MH  - Humans
MH  - Immunoprecipitation
MH  - Mitogens/*metabolism
MH  - Mutation/genetics
MH  - Phospholipase D/genetics/*metabolism
MH  - Protein Binding
MH  - Protein Kinases/genetics/*metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Transfection
EDAT- 2006/07/14 09:00
MHDA- 2007/02/06 09:00
CRDT- 2006/07/14 09:00
PHST- 2006/04/26 00:00 [received]
PHST- 2006/05/11 00:00 [revised]
PHST- 2006/05/11 00:00 [accepted]
PHST- 2006/07/14 09:00 [pubmed]
PHST- 2007/02/06 09:00 [medline]
PHST- 2006/07/14 09:00 [entrez]
AID - S0898-6568(06)00115-X [pii]
AID - 10.1016/j.cellsig.2006.05.021 [doi]
PST - ppublish
SO  - Cell Signal. 2006 Dec;18(12):2283-91. doi: 10.1016/j.cellsig.2006.05.021. Epub 
      2006 Jun 3.