Effects of PIP2 hydrolysis (Homo sapiens)

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Curation Tags


Hydrolysis of phosphatidyl inositol-bisphosphate (PIP2) by phospholipase C (PLC) produces diacylglycerol (DAG) and inositol triphosphate (IP3). Both are potent second messengers. IP3 diffuses into the cytosol, but as DAG is a hydrophobic lipid it remains within the plasma membrane. IP3 stimulates the release of calcium ions from the smooth endoplasmic reticulum, while DAG activates the conventional and unconventional protein kinase C (PKC) isoforms, facilitating the translocation of PKC from the cytosol to the plasma membrane. The effects of DAG are mimicked by tumor-promoting phorbol esters. DAG is also a precursor for the biosynthesis of prostaglandins, the endocannabinoid 2-arachidonoylglycerol and an activator of a subfamily of TRP-C (Transient Receptor Potential Canonical) cation channels 3, 6, and 7. View original pathway at:Reactome.

Ontology Tags



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  7. Mahaut-Smith MP, Sage SO, Rink TJ.; ''Receptor-activated single channels in intact human platelets.''; PubMed
  8. Chau LY, Tai HH.; ''Release of arachidonate from diglyceride in human platelets requires the sequential action of a diglyceride lipase and a monoglyceride lipase.''; PubMed
  9. Newton AC.; ''Lipid activation of protein kinases.''; PubMed
  10. Berridge MJ, Lipp P, Bootman MD.; ''The versatility and universality of calcium signalling.''; PubMed
  11. Wang J, Ueda N.; ''Biology of endocannabinoid synthesis system.''; PubMed
  12. Carrasco S, Mérida I.; ''Diacylglycerol, when simplicity becomes complex.''; PubMed
  13. Savinainen JR, Saario SM, Laitinen JT.; ''The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoylglycerol signalling through cannabinoid receptors.''; PubMed
  14. Moriyama T, Urade R, Kito M.; ''Purification and characterization of diacylglycerol lipase from human platelets.''; PubMed
  15. van Blitterswijk WJ, Houssa B.; ''Properties and functions of diacylglycerol kinases.''; PubMed
  16. Schaap D, de Widt J, van der Wal J, Vandekerckhove J, van Damme J, Gussow D, Ploegh HL, van Blitterswijk WJ, van der Bend RL.; ''Purification, cDNA-cloning and expression of human diacylglycerol kinase.''; PubMed


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83152view10:10, 18 November 2015ReactomeTeamVersion54
81503view13:02, 21 August 2015ReactomeTeamVersion53
76979view08:26, 17 July 2014ReactomeTeamFixed remaining interactions
76684view12:05, 16 July 2014ReactomeTeamFixed remaining interactions
76011view10:07, 11 June 2014ReactomeTeamRe-fixing comment source
75719view11:08, 10 June 2014ReactomeTeamReactome 48 Update
75071view13:58, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74716view08:47, 30 April 2014ReactomeTeamReactome46
42032view21:51, 4 March 2011MaintBotAutomatic update
39835view05:52, 21 January 2011MaintBotNew pathway

External references

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NameTypeDatabase referenceComment
GlycerolMetaboliteCHEBI:17754 (ChEBI)
DGKZ ProteinQ13574 (Uniprot-TrEMBL)
ITPR2 ProteinQ14571 (Uniprot-TrEMBL)
DGKB ProteinQ9Y6T7 (Uniprot-TrEMBL)
ITPR3 ProteinQ14573 (Uniprot-TrEMBL)
IP3R tetramerComplexR-HSA-418292 (Reactome)
ITPR1 ProteinQ14643 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
I(1,4,5)P3MetaboliteCHEBI:16595 (ChEBI)
DGKG ProteinP49619 (Uniprot-TrEMBL)
IP3R tetramer:I(1,4,5)P3:4xCa2+ComplexR-HSA-139839 (Reactome)
3AGMetaboliteCHEBI:75571 (ChEBI)
I(1,4,5)P3 MetaboliteCHEBI:16595 (ChEBI)
DAGLA ProteinQ9Y4D2 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
MGLLProteinQ99685 (Uniprot-TrEMBL)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Diacylglycerol kinaseComplexR-HSA-426070 (Reactome)
CalDAG-GEFsComplexR-HSA-392488 (Reactome) Rap1 can be activated by certain GEFs that respond to calcium and diacylglycerol (CalDAG-GEFs).
DGKE ProteinP52429 (Uniprot-TrEMBL)
RASGRP2 ProteinQ7LDG7 (Uniprot-TrEMBL)
DGKK ProteinQ5KSL6 (Uniprot-TrEMBL)
RASGRP1 ProteinO95267 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
ABHD12 ProteinQ8N2K0 (Uniprot-TrEMBL)
Protein kinase C, novel isoformsComplexR-HSA-425850 (Reactome) These isoforms of PKC bind DAG and phosphatidylserine (PS), but unlike the conventional forms, do not require calcium for PS binding.
Diacylglycerol lipaseComplexR-HSA-426024 (Reactome)
PRKCD ProteinQ05655 (Uniprot-TrEMBL)
DAGLB ProteinQ8NCG7 (Uniprot-TrEMBL)
PRKCE ProteinQ02156 (Uniprot-TrEMBL)
AAMetaboliteCHEBI:15843 (ChEBI)
PRKCH ProteinP24723 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
PRKCQ ProteinQ04759 (Uniprot-TrEMBL)
1,2-diacyl-glycerol 3-phosphateCHEBI:29089 (ChEBI)
Protein kinase C, novel isoforms:DAGComplexR-HSA-426071 (Reactome)
DGKA ProteinP23743 (Uniprot-TrEMBL)
DAG MetaboliteCHEBI:17815 (ChEBI)
DGKD ProteinQ16760 (Uniprot-TrEMBL)
TRPC3/6/7ComplexR-HSA-426176 (Reactome)
DGKH ProteinQ86XP1 (Uniprot-TrEMBL)
TRPC3(1-848) ProteinQ13507 (Uniprot-TrEMBL)
DGKI ProteinO75912 (Uniprot-TrEMBL)
TRPC7 ProteinQ9HCX4 (Uniprot-TrEMBL)
DGKQ ProteinP52824 (Uniprot-TrEMBL)
TRPC6 ProteinQ9Y210 (Uniprot-TrEMBL)
CalDAG-GEFs:DAG:Ca2+ComplexR-HSA-392841 (Reactome)
DAG-activated TRPC3/6/7ComplexR-HSA-426179 (Reactome)
H+MetaboliteCHEBI:15378 (ChEBI)
2AGMetaboliteCHEBI:52392 (ChEBI)
ABHD6,12ComplexR-HSA-5694453 (Reactome)
Fatty AcidCHEBI:35366 (ChEBI)
ABHD6 ProteinQ9BV23 (Uniprot-TrEMBL)
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