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.
- beta: PLCB1, PLCB2, PLCB3, PLCB4
- gamma: PLCG1, PLCG2
- delta: PLCD1, PLCD3, PLCD4
- epsilon: PLCE1
- eta: PLCH1, PLCH2
- zeta: PLCZ1
- phospholipase C-like: PLCL1, PLCL2
- 5-HT2 serotonergic receptors
- α1 (Alpha-1) adrenergic receptors
- Calcitonin receptors
- H1 histamine receptors
- Metabotropic glutamate receptors, Group I
- M1, M3, and M5 muscarinic receptors
- Thyroid-Releasing Hormone receptor in anterior pituitary gland
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.
PLC cleaves the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) 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, particularly calcium channels in the smooth 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.
Additionally, phospholipase c plays an important role in the inflammation pathway. The binding of agonists such as thrombin, epinephrine, or collagen, to platelet surface receptors can trigger the activation of phospholipase C to catalyze the release of arachidonic acid from two major membrane phospholipids, phosphatidylinositol and phosphatidylcholine. Arachadonic acid can then go on into the cyclooxygenase pathway (producing prostoglandins (PGE1, PGE2, PGF2), prostacyclins (PGI2), or thromboxanes (TXA2)), and the lipoxygenase pathway (producing leukotrienes (LTB4, LTC4, LTD4, LTE4)).
In other organisms
- Phosphoinositide phospholipase C EC 22.214.171.124 The main form found in eukaryotes, especially mammals.
- Zinc-dependent phospholipase C family of bacterial enzymes EC 126.96.36.199 that includes the alpha toxins of C. perfringens (also known as lecithinase), P. aeruginosa, and S. aureus.
- Phosphatidylinositol diacylglycerol-lyase EC 188.8.131.52 Another related bacterial enzyme
- Glycosylphosphatidylinositol diacylglycerol-lyase EC 184.108.40.206 A trypanosomal enzyme.
- Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300. ISBN 1-4160-2328-3. Page 104
- GeneGlobe -> GHRH Signaling Retrieved on May 31, 2009
- Alberts B, Lewis J, Raff M, Roberts K, Walter P (2002). Molecular biology of the cell (4th ed.). New York: Garland Science. ISBN 0-8153-3218-1.