PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals

mTOR signaling: PLD takes center stage

“…[73][74][75] PLD2 is shown to interact with Raptor through this motif, and PLD2 activation of mTORC1 signaling is dependent on both its TOS motif (therefore Raptor interaction) and its lipase activity (therefore PA production). 36 Contrary to our observations, Ha et al, found that knockdown of PLD2, but not PLD1, inhibits mTORC1 activation. 36 The reason for this discrepancy remains unclear, but it could be attributed to different knockdown conditions and/or cell lines (or sub-cell lines).…”

“…36 Contrary to our observations, Ha et al, found that knockdown of PLD2, but not PLD1, inhibits mTORC1 activation. 36 The reason for this discrepancy remains unclear, but it could be attributed to different knockdown conditions and/or cell lines (or sub-cell lines). It should not be too surprising to find regulatory mechanisms at the biochemical level common for both PLD1 and PLD2, if one considers the high levels of structural similarity between the two proteins.…”

“…For instance, overexpression of recombinant PLD2 has been reported to activate mTORC1 in MCF-7 breast cancer cells 25 as well as COS-7 cells. 28,36 It is noteworthy that in the Lehman et al, report recombinant PLD2 is shown to co-localize with S6K1 in the perinuclear region. 28 This contradicts the predominant plasma membrane localization of PLD2 observed by others, 69,71 and raises a concern for potential artifact of protein overexpression.…”

“…34), whereas PLD knockdown blocks mitogenic activation of mTORC1 signaling. 32,35,36 The small G protein Cdc42 had long been known as an activator of S6K1 with an exact mechanism yet to be determined, 37 and now PLD1 has been revealed as a molecular link between Cdc42 and mTORC1. 32 In addition to PLD, two other PA-producing enzymes-lysophosphatidic acid acyltransferase (LPAAT) and diacylglycerol kinase (DGK)-have also been shown to regulate mTOR signaling through PA, 38,39 further validating the link between PA and mTOR.…”

PLD2 (phospholipase D2)

“…Cell growth signaling Cells regulate cellular homeostasis by using extracellular nutrients and growth signals, and malfunctions in this process cause severe diseases, such as, cancer and diabetes. PLD2 acts as a key regulator of growth signaling mainly via the control of the mammalian target of rapamycin (mTOR), which is a key target for cancer treatment (Ha et al, 2006). Both PLD2 and PA can affect mTor signaling.…”