Enzymes, proteins, riboproteins and signaling pathways.


Phospholipases are enzymes that hydrolyze specific ester bonds in phosphoglycerides or glycerophosphatidates, converting the phospholipids into fatty acids and other lipophilic substances. Phospholipases are involved in signaling cascades.

Phospholipase A1 hydrolyzes the acyl group attached to the 1-position, while phospholipase A2 hydrolyzes the acyl group attached to the 2-position to form fatty acid and lysophospholipid products. Phospholipase A2 is responsible for the release of arachidonic acid from membranes (flow diagram PLA2 pathway). Arachidonic acid is a signalling molecule and is the precursor for eicosanoid signaling molecules, which include leukotrienes and prostaglandins. Some eicosanoids are synthesized from diacylglycerol, and are released from the lipid bilayer by phospholipase C. [] 3D phospholipase-C /PDGF-receptor []

Phospholipases and phospholipids participate in transmission of ligand-receptor induced signals from the plasma membrane to intracellular proteins, primarily PKC, which is maximally active in the presence of calcium ion and diacylglycerol. PKC activity is mediated by receptors that are coupled to activation of phospholipase C-γ (PLC-γ), which contains SH2 domains that enable it to interact with tyrosine phosphorylated RTKs. PI-3K is tyrosine phosphorylated and activated by various RTKs and receptor-associated PTKs. PI-3K is activated by the PDGF, EGF, insulin, IGF-1, HGF and NGF receptors. The p85 subunit of PI-3K is activated by tyrosine phosphorylation, but only the 110 kDa subunit is enzymatically active.

Phospholipases D and A2 (PLD, PLA2) sustain the activation of PKC through their hydrolysis of membrane phosphatidylcholine (PC). Activation of PLC-γ results in hydrolysis of membrane phosphatidylinositol bisphosphate (PIP2), which leads to an elevation of intracellular second messengers, diacylglycerol (DAG) and inositol trisphosphate (IP3), which interact with intracellular membrane receptors to effect release of stored calcium ions (PKC is maximally active in the presence of calcium ion and diacylglycerol).

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