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'''<u>PHOSPHOLIPASE C, BETA-4; PLCB4</u>'''
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>.


Phospholipase C (PLC) catalyzes [[Hydrolysis|hydrolysis]] of a plasma membrane [[Phospholipid|phospholipid,]] phosphatidylinositol 4,5-bisphosphate, generating 2 second messengers, the water soluble 1,4,5-inositol trisphosphate and the membrane-associated 1,2-diacylglycerol. In mammalian tissues, several groups of PLCs have been characterized, including PLC-beta, and each group contains at least 3 [[Isoforms|isoforms]]. These proteins are single polypeptides, ranging in molecular mass from 65 to 154 kD (review by Alvarez et al., 1995) <ref>http://www.ncbi.nlm.nih.gov/omim/600810</ref>.<br>
There are some studies that show that this enzyme has five groups, each group contains at least two isoforms.  


Phosphatidylinositol-specific phospholipase C (EC 3.1.4.11), a eukaryotic[[Intracellular|intracellular enzyme]], plays an important role in signal transduction processes (PUBMED:1849017). It catalyzes the hydrolysis of 1-phosphatidyl-D-myo-inositol-3,4,5-triphosphate into the second messenger molecules diacylglycerol and inositol-1,4,5-triphosphate. This catalytic process is tightly regulated by reversible phosphorylation and binding of regulatory proteins (PUBMED:1419362), (PUBMED:1319994), (PUBMED:1335185). In mammals, there are at least 6 different isoforms of PI-PLC, they differ in their domain structure, their regulation, and their tissue distribution. Lower eukaryotes also possess multiple isoforms of PI-PLC. All eukaryotic PI-PLCs contain two regions of homology, sometimes referred to as the 'X-box' and 'Y-box'. The order of these two regions is always the same (NH2-X-Y-COOH), but the spacing is variable. In most isoforms, the distance between these two regions is only 50-100 residues but in the gamma isoforms one PH domain, two SH2 [[Domains|domains,]] and one SH3 domain are inserted between the two PLC-specific domains. The two conserved regions have been shown to be important for the catalytic activity. By profile analysis, we could show that sequences with significant similarity to the X-box domain occur also in prokaryotic and trypanosome PI-specific phospholipases C. Apart from this region, the [[Prokaryotic|prokaryotic]] enzymes show no similarity to their [[Eukaryotic|eukaryotic]] counterparts
#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


<u>'''Phosphoinositide-specific phospholipase C, efhand-like <br>'''</u>Members of this family are predominantly found in phosphoinositide-specific phospholipase C. They adopt a structure consisting of a core of four [[Alpha helices|alpha helices]], in an EF like fold, and are required for functioning of the enzyme <ref>http://pfam.sanger.ac.uk/family/PF09279.4</ref>.<br>
Most of them differ in their activation. Because they are controlled by different [[Receptors|receptors]].  


<u>'''Cloning and characterization of the human phosphoinositide-specific phospholipase C-beta 1 (PLC beta 1).<br>'''</u>
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:


Four mammalian isozymes are known (PLCβ1–4), which differ in their function and expression patterns in vivo. We have characterized the human PLCβ1 genomic locus (PLCβ1), cloned two distinct PLCβ1 cDNAs (PLCβ1a and b) and analysed their respective expression patterns in a comprehensive panel of human tissues using quantitative TaqMan technology. The two cDNAs derive from transcripts generated through alternative splicing at their 3′ end, and are predicted to encode for PLCβ1 isoforms differing at their carboxy-terminus. The human PLCβ1 isoforms are co-expressed in the same tissues with a distinctly CNS-specific profile of expression. Quantitative differences in PLCβ1 isoform expression levels are observed in some tissues. Transient expression of epitope-tagged versions of the two isoforms followed by immunofluorescence revealed localization of the proteins to the [[Cytoplasm|cytoplasm]] and the inner side of the [[Cell membrane|cell membrane]]. Finally, we characterized the structure of the PLCβ1 locus and confirmed its mapping to human chromosome 20 <ref>Andrea Caricasole, Cinzia Sala, Renza Roncarati, Elisa Formenti, Georg C. Terstappen, Cloning and characterization of the human phosphoinositide-specific phospholipase C-beta 1 (PLC[beta]1), Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, Volume 1517, Issue 1, 15 December 2000, Pages 63-72, ISSN 0167-4781, DOI: 10.1016/S0167-4781(00)00260-8.fckLR(http://www.sciencedirect.com/science/article/B6T1V-41WBB32-7/2/c29bb149393824b8e3937b51c705b85e)</ref>.<br>
#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.
 
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  ===


<references />[http://www.ncbi.nlm.nih.gov/omim/600810 http://www.ncbi.nlm.nih.gov/omim/600810] <br><references />[http://pfam.sanger.ac.uk/family/PF09279.4 http://pfam.sanger.ac.uk/family/PF09279.4]
<references />
 
<br><references />Andrea Caricasole, Cinzia Sala, Renza Roncarati, Elisa Formenti, Georg C. Terstappen, Cloning and characterization of the human phosphoinositide-specific phospholipase C-beta 1 (PLC[beta]1), Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, Volume 1517, Issue 1, 15 December 2000, Pages 63-72, ISSN 0167-4781, DOI: 10.1016/S0167-4781(00)00260-8.fckLR
 
<references />[http://www.sciencedirect.com/science/article/B6T1V-41WBB32-7/2/c29bb149393824b8e3937b51c705b85e http://www.sciencedirect.com/science/article/B6T1V-41WBB32-7/2/c29bb149393824b8e3937b51c705b85e])<br><references />http://smart.embl-heidelberg.de/smart/do_annotation.pl?DOMAIN=PLCXc&amp;START=316&amp;END=467&amp;E_VALUE=2.85e-74&amp;TYPE=SMART&amp;BLAST=EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEEEPVITHGFTMTTEISFKEVIEAIAECAFKTSPFPILLSFENHVDSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVKNK

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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