Phospholipase C

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Phospholipase C, PLC is an enzyme that produces two second messengers inositol 1, 4, 5-triphosphate (IP3) and diacylglycerol (DAG) by cleavage of inositol phospolipids. IP3 in turn triggers the release of calcium ions from the endoplasmic reticulum ( or sarcoplasmic reticulum in muscle cells). DAG activates protein kinase C (PKC)[1][2][3][4].

There are some studies that show that this enzyme has five groups, each group contains at least two isoforms.

  1. Eta is a superfamily of 1,2
  2. Beta 1,2,3 and 4 key step in the intracellular transduction of many extracellular signals, are regulated by heterotrimeric G protein-coupled receptors, Gq activates inositol phospholipid signalling pathway which in turn will activate PLC-beta enzyme.
  3. Delta 1,2,3
  4. Gamma 1,2 enzymes are controlled by receptor tyrosine kinases.
  5. Zeta 1

Most of them differ in their activation. Because they are controlled by different receptors.

Phospholipase C is a plasma membrane bound enzyme and is activated by G- protein linked signalling in a similar process to the activation of adenylyl cyclase. Once the G protein has been stimulated it activates phospholipase C which cleaves a phospholipid called phosphatidylinositol 4,5- biphosphate found in the plasma membrane lipid bilayer [5]. This results in two products: inositol 1,4,5 triphosphate (IP3) and diacylglycerol (DAG). IP3 diffuses into the cytosol untill it reaches the endoplasmic reticulum where it opens calcium channels causing a release of Ca2+ into the cytosol. This effect can be reversed in three different ways:

  1. IP3 can form IP2 via dephosphorylation.
  2. IP3 can be phosphorylated to form IP4
  3. Ca2+ is pumped out rapidly.

The other product, DAG remains in the plasma membrane due to its hydrophobic fatty chains. DAG activates protein kinase C (PKC) which then phosphorylates target proteins. PKC is activated by Ca2+ and diacylglycerol and is therefore called a conventional PKC[6]. DAG can also remain in the plasma membrane as it can be cleaved again with the product acting as a signalling molecule[7].

References

  1. Patricia A. Hartz,2003, PHOSPHOLIPASE C, ZETA-1; PLCZ1. OMIM(MIM ID *608075) [online] available at http://www.ncbi.nlm.nih.gov/omim/608075 [Accessed 13 November2010].
  2. Fukami K, et al.,2010 oct, Phospholipase C is a key enzyme regulating intracellular calcium and modulating the phosphoinositide balance. Prog Lipid Res. 49(4):429-37 [online] available at http://www.ncbi.nlm.nih.gov/pubmed [Accessed 13 November2010].
  3. Wang J, et al., 2010 Oct;30. Phosphorylation of G protein-coupled receptor kinase 2-interacting protein 1 tyrosine 392 is required for phospholipase C-gamma activation and podosome formation in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol, (10),pp.1976-82 [online] available at http://www.ncbi.nlm.nih.gov/pubmed/20689073 [Accessed 13 November2010].
  4. Bruce, A. et al., 2008. Molecular biology of the cell, 5th ed, New York: Garland science, pp.909.
  5. Bruce Alberts,Alexander Johnson,Julian Lewis, Martin Raff,Keith Roberts and Peter Walter (2008) Molecular Biology of the cell, 5th edition USA: Garland Science page 909
  6. Alberts et Al. Molecular Biology of the cell, 5th edition USA: Garland Science page 911
  7. Alberts et al, Molecular Biology of the cell,5th edition, USA: Garland Science page 910
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