Phospholipase C



Phospholipase C (PLC) is a class of enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role in eukaryotic cell physiology, in particular signal transduction pathways. Thirteen kinds of mammalian phospholipase C are classified into six isotypes (β, γ, δ, ε, ζ, η) according to structure.

Mammalian variants

 * beta: PLCB1, PLCB2, PLCB3, PLCB4
 * gamma: PLCG1, PLCG2
 * delta: PLCD1, PLCD3, PLCD4
 * epsilon: PLCE1
 * eta: PLCH1, PLCH2
 * zeta: PLCZ1
 * phospholipase C-like: PLCL1, PLCL2

Activation
Receptors that activate this pathway are mainly G protein-coupled receptors coupled to the Gαq subunit, including:
 * 5-HT2 serotonergic receptors
 * α1 (Alpha-1) adrenergic receptors
 * Kappa opioid receptors
 * Calcitonin receptors
 * H1 histamine receptors
 * Metabotropic glutamate receptors, Group I
 * M 1, M 3, and M 5 muscarinic receptors

Other, minor, activators than Gαq are:
 * MAP kinase. Activators of this pathway include PDGF and FGF.
 * βγ-complex of heterotrimeric G-proteins, as in a minor pathway of growth hormone release by growth hormone-releasing hormone.

Effects
PLC cleaves a phospholipid. Phosphatidylinositol 4,5-bisphosphate (PIP2) is cleaved into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG remains bound to the membrane, and IP3 is released as a soluble structure into the cytosol. IP3 then diffuses through the cytosol to bind to IP3 receptors, particular calcium channels in the endoplasmic reticulum (ER). This causes the cytosolic concentration of calcium to increase, causing a cascade of intracellular changes and activity. In addition, calcium and DAG together work to activate protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. End effects include taste, tumor promotion, etc.

In other organisms
Other phospholipase C enzymes have been identified in bacteria and in trypanosomes, each with its own EC number
 * Phosphoinositide phospholipase C The main form found in eukaryotes, especially mammals.
 * Zinc-dependent phospholipase C family of bacterial enzymes that includes alpha toxins
 * Phosphatidylinositol diacylglycerol-lyase Another related bacterial enzyme
 * Glycosylphosphatidylinositol diacylglycerol-lyase A trypanosomal enzyme.