Phospholipase C: Difference between revisions

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'''phospholipase C''', PLC is an [[Enzyme|enzyme]] that produces two second messengers IP3 and diacylglycerol (DAG)&nbsp;by cleavage of inositol phospolipids. IP3 in turn will trigger the release of calcium from [[Intracellular|intracellular stores]], and DAG is going to activate [[Protein kinase C|protein kinase C ]](PKC).<br>There is some studies that shows that this enzyme has five groups, each group contains at least two isoforms .<br>1.Eta is a superfamily of 1,2<br>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.<br><br>3.Delta 1,2,3 <br>4.Gamma 1,2 enzymes are controlled by receptor [[tyrosine kinases|tyrosine kinases]]. <br>5.Zeta 1<br>
Phospholipase C, PLC is an [[Enzyme|enzyme]] that produces two second messengers inositol 1, 4, 5-triphosphate ([[Ip3|IP]]<sub>[[Ip3|3]]</sub>) and [[Diacylglycerol|diacylglycerol]] ([[Diacylglycerol|DAG]]) by cleavage of inositol phospolipids. [[Ip3|IP]]<sub>[[Ip3|3]]</sub> in turn triggers the release of [[Calcium ions|calcium ions]] from the [[Endoplasmic Reticulum|endoplasmic reticulum]] ( or [[Sarcoplasmic Reticulum|sarcoplasmic reticulum]] in muscle cells). [[Diacylglycerol|DAG]] activates [[Protein kinase C|protein kinase C]] ([[Protein kinase C|PKC]])<ref>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].</ref><ref>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].</ref><ref>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].</ref><ref>Bruce, A. et al., 2008. Molecular biology of the cell, 5th ed, New York: Garland science, pp.909.</ref>.  


Most of them differ in their activation. Because, They are controlled by different [[Receptors|receptors]]. <br>
There are some studies that show that this enzyme has five groups, each group contains at least two isoforms.  


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


<references />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].  
Most of them differ in their activation. Because they are controlled by different [[Receptors|receptors]].  


<br>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].<br>
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|adenylyl cyclase]]. Once the G protein has been stimulated it activates phospholipase C which cleaves a phospholipid called [[Phosphatidylinositol 4,5-bisphosphate|phosphatidylinositol 4,5- biphosphate]] found in the plasma membrane lipid bilayer <ref>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</ref>. This results in two products: [[Inositol 1,4,5 trisphosphate|inositol 1,4,5 triphosphate]] (IP<sub>3</sub>) and [[Diacylglycerol|diacylglycerol]] (DAG). IP<sub>3 </sub>diffuses into the cytosol untill it reaches the [[Endoplasmic reticulum|endoplasmic reticulum]] where it opens calcium channels causing a release of Ca<sup>2+</sup> into the cytosol. This effect can be reversed in three different ways:


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].  
#IP<sub>3 </sub>can form IP<sub>2 </sub>via dephosphorylation.  
#IP<sub>3 </sub>can be phosphorylated to form IP<sub>4</sub>
#Ca<sup>2+</sup> is pumped out rapidly.


Bruce, A. et al., 2008. Molecular biology of the cell, 5th ed, New York: Garland science, pp.909.<references /><br>
The other product, DAG remains in the [[Plasma membrane|plasma membrane]] due to its [[Hydrophobic|hydrophobic]] fatty chains. DAG activates [[Protein kinase C|protein kinase C (PKC)]] which then phosphorylates target [[Proteins|proteins]]. PKC is activated by Ca<sup>2+ </sup>and diacylglycerol and is therefore called a conventional PKC<ref>Alberts et Al. Molecular Biology of the cell, 5th edition USA: Garland Science page 911</ref>. DAG can also remain in the plasma membrane as it can be cleaved again with the product acting as a signalling molecule<ref>Alberts et al, Molecular Biology of the cell,5th edition, USA: Garland Science page 910</ref>.  
 
=== References  ===
 
<references />

Latest revision as of 17:31, 19 November 2017

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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