- Home
- Targets
- Enzymes
- Glycerophospholipid turnover
- Phosphoinositide-specific phospholipase C
Phosphoinositide-specific phospholipase C C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
Phosphoinositide-specific phospholipase C (PLC, EC 3.1.4.11), catalyses the hydrolysis of PIP2 to IP3 and 1,2-diacylglycerol, each of which have major second messenger functions. Two domains, X and Y, essential for catalytic activity, are conserved in the different forms of PLC. Isoforms of PLC-β are activated primarily by G protein-coupled receptors through members of the Gq/11 family of G proteins. The receptor-mediated activation of PLC-γ involves their phosphorylation by receptor tyrosine kinases (RTK) in response to activation of a variety of growth factor receptors and immune system receptors. PLC-ε1 may represent a point of convergence of signalling via both G protein-coupled and catalytic receptors. Ca2+ ions are required for catalytic activity of PLC isoforms and have been suggested to be the major physiological form of regulation of PLC-δ activity. PLC has been suggested to be activated non-selectively by the small molecule m3M3FBS [2], although this mechanism of action has been questioned [12]. The aminosteroid U73122 has been described as an inhibitor of phosphoinositide-specific PLC [20], although its selectivity among the isoforms is untested and it has been reported to occupy the H1 histamine receptor [8].
Enzymes
Targets of relevance to immunopharmacology are highlighted in blue
|
PLCβ1 C Show summary »« Hide summary
|
|||||||||||||||||||||
|
PLCβ2 C Show summary »« Hide summary
|
|||||||||||||||||||||
|
PLCβ3 C Show summary »« Hide summary
|
|||||||||||||||||||||
|
PLCβ4 C Show summary »« Hide summary
|
|||||||||||||||||||||
|
PLCγ1
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||
|
PLCγ2
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||
|
PLCδ1 C Show summary »« Hide summary
|
|||||||||||||||||||||
|
PLCδ3 C Show summary »« Hide summary
|
|||||||||||||||||||||
|
PLCδ4 C Show summary »« Hide summary
|
|||||||||||||||||||||
|
PLCε1 C Show summary »« Hide summary
|
|||||||||||||||||||||
|
PLCζ1 C Show summary »« Hide summary
|
|||||||||||||||||||||
|
PLCη1 C Show summary »« Hide summary
|
|||||||||||||||||||||
|
PLCη2 C Show summary »« Hide summary
|
Further reading
* Key recommended reading is highlighted with an asterisk
Cocco L, Follo MY, Manzoli L, Suh PG. (2015) Phosphoinositide-specific phospholipase C in health and disease. J Lipid Res, 56 (10): 1853-60. [PMID:25821234]
Cockcroft S, Raghu P. (2016) Topological organisation of the phosphatidylinositol 4,5-bisphosphate-phospholipase C resynthesis cycle: PITPs bridge the ER-PM gap. Biochem J, 473 (23): 4289-4310. [PMID:27888240]
* Filkin SY, Lipkin AV, Fedorov AN. (2020) Phospholipase Superfamily: Structure, Functions, and Biotechnological Applications. Biochemistry (Mosc), 85 (Suppl 1): S177-S195. [PMID:32087059]
* Katan M, Cockcroft S. (2020) Phospholipase C families: Common themes and versatility in physiology and pathology. Prog Lipid Res, 80: 101065. [PMID:32966869]
Litosch I. (2015) Regulating G protein activity by lipase-independent functions of phospholipase C. Life Sci, 137: 116-24. [PMID:26239437]
* Nakamura Y, Fukami K. (2017) Regulation and physiological functions of mammalian phospholipase C. J Biochem, 161 (4): 315-321. [PMID:28130414]
Swann K, Lai FA. (2016) The sperm phospholipase C-ΞΆ and Ca2+ signalling at fertilization in mammals. Biochem Soc Trans, 44 (1): 267-72. [PMID:26862214]
References
1. Bae YS, Cantley LG, Chen CS, Kim SR, Kwon KS, Rhee SG. (1998) Activation of phospholipase C-gamma by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem, 273 (8): 4465-9. [PMID:9468499]
2. Bae YS, Lee TG, Park JC, Hur JH, Kim Y, Heo K, Kwak JY, Suh PG, Ryu SH. (2003) Identification of a compound that directly stimulates phospholipase C activity. Mol Pharmacol, 63 (5): 1043-50. [PMID:12695532]
3. Camps M, Carozzi A, Schnabel P, Scheer A, Parker PJ, Gierschik P. (1992) Isozyme-selective stimulation of phospholipase C-beta 2 by G protein beta gamma-subunits. Nature, 360 (6405): 684-6. [PMID:1465133]
4. Carozzi A, Camps M, Gierschik P, Parker PJ. (1993) Activation of phosphatidylinositol lipid-specific phospholipase C-beta 3 by G-protein beta gamma subunits. FEBS Lett, 315 (3): 340-2. [PMID:8380773]
5. Haber MT, Fukui T, Lebowitz MS, Lowenstein JM. (1991) Activation of phosphoinositide-specific phospholipase C delta from rat liver by polyamines and basic proteins. Arch Biochem Biophys, 288 (1): 243-9. [PMID:1654825]
6. Hepler JR, Kozasa T, Smrcka AV, Simon MI, Rhee SG, Sternweis PC, Gilman AG. (1993) Purification from Sf9 cells and characterization of recombinant Gq alpha and G11 alpha. Activation of purified phospholipase C isozymes by G alpha subunits. J Biol Chem, 268 (19): 14367-75. [PMID:8314796]
7. Homma Y, Emori Y. (1995) A dual functional signal mediator showing RhoGAP and phospholipase C-delta stimulating activities. EMBO J, 14 (2): 286-91. [PMID:7835339]
8. Hughes SA, Gibson WJ, Young JM. (2000) The interaction of U-73122 with the histamine H1 receptor: implications for the use of U-73122 in defining H1 receptor-coupled signalling pathways. Naunyn Schmiedebergs Arch Pharmacol, 362 (6): 555-8. [PMID:11138848]
9. Illenberger D, Walliser C, Nurnberg B, Diaz Lorente M, Gierschik P. (2003) Specificity and structural requirements of phospholipase C-beta stimulation by Rho GTPases versus G protein beta gamma dimers. J Biol Chem, 278 (5): 3006-14. [PMID:12441352]
10. Illenberger D, Walliser C, Strobel J, Gutman O, Niv H, Gaidzik V, Kloog Y, Gierschik P, Henis YI. (2003) Rac2 regulation of phospholipase C-beta 2 activity and mode of membrane interactions in intact cells. J Biol Chem, 278 (10): 8645-52. [PMID:12509427]
11. Jhon DY, Lee HH, Park D, Lee CW, Lee KH, Yoo OJ, Rhee SG. (1993) Cloning, sequencing, purification, and Gq-dependent activation of phospholipase C-beta 3. J Biol Chem, 268 (9): 6654-61. [PMID:8454637]
12. Krjukova J, Holmqvist T, Danis AS, Akerman KE, Kukkonen JP. (2004) Phospholipase C activator m-3M3FBS affects Ca2+ homeostasis independently of phospholipase C activation. Br J Pharmacol, 143 (1): 3-7. [PMID:15302681]
13. Lee CH, Park D, Wu D, Rhee SG, Simon MI. (1992) Members of the Gq alpha subunit gene family activate phospholipase C beta isozymes. J Biol Chem, 267 (23): 16044-7. [PMID:1322889]
14. Meldrum E, Kriz RW, Totty N, Parker PJ. (1991) A second gene product of the inositol-phospholipid-specific phospholipase C delta subclass. Eur J Biochem, 196 (1): 159-65. [PMID:1848183]
15. Murthy SN, Lomasney JW, Mak EC, Lorand L. (1999) Interactions of G(h)/transglutaminase with phospholipase Cdelta1 and with GTP. Proc Natl Acad Sci USA, 96 (21): 11815-9. [PMID:10518533]
16. Park D, Jhon DY, Lee CW, Lee KH, Rhee SG. (1993) Activation of phospholipase C isozymes by G protein beta gamma subunits. J Biol Chem, 268 (7): 4573-6. [PMID:8383116]
17. Pawelczyk T, Lowenstein JM. (1992) Regulation of phospholipase C delta activity by sphingomyelin and sphingosine. Arch Biochem Biophys, 297 (2): 328-33. [PMID:1497353]
18. Piechulek T, Rehlen T, Walliser C, Vatter P, Moepps B, Gierschik P. (2005) Isozyme-specific stimulation of phospholipase C-gamma2 by Rac GTPases. J Biol Chem, 280 (47): 38923-31. [PMID:16172125]
19. Reynisson J, Court W, O'Neill C, Day J, Patterson L, McDonald E, Workman P, Katan M, Eccles SA. (2009) The identification of novel PLC-gamma inhibitors using virtual high throughput screening. Bioorg Med Chem, 17 (8): 3169-76. [PMID:19303309]
20. Smith RJ, Sam LM, Justen JM, Bundy GL, Bala GA, Bleasdale JE. (1990) Receptor-coupled signal transduction in human polymorphonuclear neutrophils: effects of a novel inhibitor of phospholipase C-dependent processes on cell responsiveness. J Pharmacol Exp Ther, 253 (2): 688-97. [PMID:2338654]
21. Smrcka AV, Hepler JR, Brown KO, Sternweis PC. (1991) Regulation of polyphosphoinositide-specific phospholipase C activity by purified Gq. Science, 251 (4995): 804-7. [PMID:1846707]
22. Song C, Hu CD, Masago M, Kariyai K, Yamawaki-Kataoka Y, Shibatohge M, Wu D, Satoh T, Kataoka T. (2001) Regulation of a novel human phospholipase C, PLCepsilon, through membrane targeting by Ras. J Biol Chem, 276 (4): 2752-7. [PMID:11022048]
23. Walliser C, Retlich M, Harris R, Everett KL, Josephs MB, Vatter P, Esposito D, Driscoll PC, Katan M, Gierschik P et al.. (2008) rac regulates its effector phospholipase Cgamma2 through interaction with a split pleckstrin homology domain. J Biol Chem, 283 (44): 30351-62. [PMID:18728011]
24. Wing MR, Bourdon DM, Harden TK. (2003) PLC-epsilon: a shared effector protein in Ras-, Rho-, and G alpha beta gamma-mediated signaling. Mol Interv, 3 (5): 273-80. [PMID:14993441]
25. Zhou Y, Wing MR, Sondek J, Harden TK. (2005) Molecular cloning and characterization of PLC-eta2. Biochem J, 391 (Pt 3): 667-76. [PMID:16107206]
How to cite this family page
Database page citation:
Phosphoinositide-specific phospholipase C. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=274.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License
A series of PLC-like proteins (PLCL1, Q15111; PLCL2, Q9UPR0 and PLCH1, Q4KWH8) form a family with PLCδ and PLCζ1 isoforms, but appear to lack catalytic activity.
PLC-δ2 has been cloned from bovine sources [14].