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PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals.
Sang Hoon Ha1, Do-Hyung Kim, Il-Shin Kim
1Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbook 790-784, Republic of Korea.
Cellular Signalling
|July 14, 2006
Summary
Phospholipase D2 (PLD2) is crucial for activating the master cell growth controller mTOR, sensing signals via phosphatidic acid (PA). PLD2 interacts with mTOR/raptor, requiring its enzyme activity for signal transduction.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mammalian target-of-rapamycin (mTOR) regulates cell growth and is activated by mitogenic signals.
- Phosphatidic acid (PA), a lipid second messenger, is generated by phospholipase D (PLD) and plays a role in mTOR signaling.
Purpose of the Study:
- To investigate the specific roles of PLD isozymes (PLD1 and PLD2) in mitogen-induced mTOR activation.
- To elucidate the mechanism by which PLD influences mTOR signaling.
Main Methods:
- Small interfering RNA (siRNA)-mediated knockdown of PLD1 and PLD2.
- Assessing the phosphorylation of mTOR effectors (S6K1 and 4EBP1).
- Investigating the interaction between PLD2 and mTOR/raptor complex using various PLD2 constructs.
Main Results:
- PLD2 knockdown, but not PLD1, significantly reduced mTOR activation markers (S6K1 and 4EBP1 phosphorylation).
- Exogenous PA-induced mTOR activation was blocked by PLD2 knockdown.
- PLD2 forms a complex with mTOR/raptor via a TOS-like motif and requires lipase activity for mTOR activation.
Conclusions:
- PLD2 is essential for mitogen-induced mTOR activation.
- Localized PA generation by PLD2, through its interaction with mTOR/raptor, is critical for signaling.
- PLD2's enzymatic activity and its specific interaction with mTOR/raptor are required for effective mTOR activation.