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Phospholipases and PI 3-Kinase Activity

Phosphoglycerides are the starting point for the generation of several critical signaling second messengers produced by PI 3-Kinase and Phospholipase A, C or D (PLA, PLC or PLD). There are many phosphoglycerides, only PIP₂ (phosphatidylinositol 4,5-bisphosphate) is shown, and a few others are described here (see table). PIP₂ is the substrate for PI 3-Kinase and PLC. PI 3-Kinase phosphorylates PIP₂ to produce PIP₃, which is in turn the substrate for the lipid phosphatase PTEN. PLC hydrolyzes PIP₂ to produce DAG (diacylglycerol) and IP3 (inositol 1,4,5-trisphosphate). PC is the substrate for the PLAs and for PLD, which produce lyso-PC and arachidonic acid, or PA and choline, respectively. PLA isoforms recognize different sites on PC; PLA₁ removes the external fatty acid, while PLA₂ cleaves off the internal. All of the end products of PI 3-Kinase and the phospholipases are critical second messengers which stimulate downstream signal transduction pathways, or are key building blocks for other important biological processes.

 

Phosphogyceride	Abbreviation	Headgroup
Pl 4,5-biphosphate	PIP2	Inositol 4.5-bisphosphate
Pl 3,4,5-triphosphate	PIP3	Inositol 4.5-trisphosphate
Phosphatidylcholine	PC	choline
Phosphatidic acid	PA	OH

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