High resolution

Module 2: Figure PLD signalling

The phospholipase D (PLD) signalling pathway.

This signalling pathway depends upon the enzyme phospholipase D1 (PLD1), which associates primarily with intracellular membranes (e.g. Golgi and endosomes), but is also found in the plasma membrane. The activation of PLD1 is linked to many receptors through a number of mechanisms that may vary depending on the location and which of its many functions PLD is carrying out. One activator is protein kinase Cα (PKCα), through a mechanism that is independent of its catalytic activity. Other major regulators are various small G proteins. Arf and Rho may be activated by the lipid messenger PtdIns3,4,5-trisphosphate (PIP3) formed by the PtdIns 3-kinase signalling cassette, whereas Ral A may be activated via Ras and the GTP/GDP exchange factor Ral-GDS. In addition, PLD1 has an absolute requirement for PtdIns4,5P2 (PIP2), which may be part of a positive-feedback loop because the PtdIns4P 5-kinase (PtdIns4P-5K) is activated by phosphatidic acid (PA). The action of PA is terminated either by a PA phosphohydrolase, which removes phosphate to leave behind diacylglycerol (DAG), or by a phospholipase A2 (PLA2) to produce lysophosphatidic acid (LPA).