Effects of PIP2 hydrolysis (Homo sapiens)

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29, 1011, 127, 813, 144-63cytosolplatelet dense tubular network lumen1,2-diacyl-glycerol 3-phosphateADPIP3 receptorTRPC3/6/7GlycerolATP1D-myo-Inositol 1,4,5-trisphosphateDiacylglycerol lipaseDAG-activated TRPC3/6/71,2-Diacylglycerol2-ArachidonoylglycerolCalDAG-GEFs:DAG:Ca2+H+Fatty AcidMonoglyceride lipaseDiacylglycerol kinaseProtein kinase C, novel isoformsProtein kinase C, novel isoforms:DAGCalciumCalDAG-GEFsCalciumIP3 receptor bound to IP3 and Ca++ArachidonateH2O1


Description

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.

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Bibliography

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  1. van Blitterswijk WJ, Houssa B.; ''Properties and functions of diacylglycerol kinases.''; PubMed Europe PMC Scholia
  2. Foskett JK, White C, Cheung KH, Mak DO.; ''Inositol trisphosphate receptor Ca2+ release channels.''; PubMed Europe PMC Scholia
  3. Mellor H, Parker PJ.; ''The extended protein kinase C superfamily.''; PubMed Europe PMC Scholia
  4. Newton AC.; ''Lipid activation of protein kinases.''; PubMed Europe PMC Scholia
  5. 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 Europe PMC Scholia
  6. Carrasco S, Mérida I.; ''Diacylglycerol, when simplicity becomes complex.''; PubMed Europe PMC Scholia
  7. Mahaut-Smith MP, Sage SO, Rink TJ.; ''Receptor-activated single channels in intact human platelets.''; PubMed Europe PMC Scholia
  8. Navia-Paldanius D, Savinainen JR, Laitinen JT.; ''Biochemical and pharmacological characterization of human α/β-hydrolase domain containing 6 (ABHD6) and 12 (ABHD12).''; PubMed Europe PMC Scholia
  9. Wang J, Ueda N.; ''Biology of endocannabinoid synthesis system.''; PubMed Europe PMC Scholia
  10. Riccio A, Mattei C, Kelsell RE, Medhurst AD, Calver AR, Randall AD, Davis JB, Benham CD, Pangalos MN.; ''Cloning and functional expression of human short TRP7, a candidate protein for store-operated Ca2+ influx.''; PubMed Europe PMC Scholia
  11. Savinainen JR, Saario SM, Laitinen JT.; ''The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoylglycerol signalling through cannabinoid receptors.''; PubMed Europe PMC Scholia
  12. 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 Europe PMC Scholia
  13. Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G.; ''Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol.''; PubMed Europe PMC Scholia
  14. Blankman JL, Simon GM, Cravatt BF.; ''A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol.''; PubMed Europe PMC Scholia
  15. Berridge MJ, Lipp P, Bootman MD.; ''The versatility and universality of calcium signalling.''; PubMed Europe PMC Scholia
  16. Moriyama T, Urade R, Kito M.; ''Purification and characterization of diacylglycerol lipase from human platelets.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114615view16:07, 25 January 2021ReactomeTeamReactome version 75
113064view11:12, 2 November 2020ReactomeTeamReactome version 74
112299view15:21, 9 October 2020ReactomeTeamReactome version 73
101197view11:09, 1 November 2018ReactomeTeamreactome version 66
100735view20:33, 31 October 2018ReactomeTeamreactome version 65
100279view19:10, 31 October 2018ReactomeTeamreactome version 64
99825view15:54, 31 October 2018ReactomeTeamreactome version 63
99382view14:32, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93885view13:42, 16 August 2017ReactomeTeamreactome version 61
93453view11:24, 9 August 2017ReactomeTeamreactome version 61
87436view13:35, 22 July 2016MkutmonOntology Term : 'hemostasis pathway' added !
87435view13:35, 22 July 2016MkutmonOntology Term : 'signaling pathway' added !
86547view09:20, 11 July 2016ReactomeTeamreactome version 56
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

DataNodes

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NameTypeDatabase referenceComment
1,2-

Diacylglycerol

Unknown17815 (ChEBI)
1,2-diacyl-glycerol 3-

phosphate

Unknown29089 (ChEBI)
1D-myo-Inositol

1,4,5-trisphosphate

Metabolite16595 (ChEBI)
2-Arachidonoylglycerol Metabolite52392 (ChEBI)
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Arachidonate Metabolite15843 (ChEBI)
CalDAG-GEFs ProteinREACT_18194 (Reactome) Rap1 can be activated by certain GEFs that respond to calcium and diacylglycerol (CalDAG-GEFs).
CalDAG-GEFs:

DAG:Ca2+

ComplexREACT_24405 (Reactome)
Calcium Metabolite29108 (ChEBI)
DAG-activated

TRPC3/6/7

ComplexREACT_24061 (Reactome)
Diacylglycerol

lipase

ProteinREACT_19676 (Reactome)
Diacylglycerol kinase ProteinREACT_20449 (Reactome)
Fatty Acid UnknownREACT_19601 (Reactome)
Glycerol Metabolite17754 (ChEBI)
H+ Metabolite15378 (ChEBI)
H2O Metabolite15377 (ChEBI)
IP3 receptor ComplexREACT_18961 (Reactome)
IP3 receptor bound

to IP3 and Ca++

ComplexREACT_4346 (Reactome)
Monoglyceride

lipase

ProteinQ99685 (UniProt)
Protein kinase C,

novel isoforms:DAG

ComplexREACT_23271 (Reactome)
Protein kinase C, novel

isoforms

ProteinREACT_22540 (Reactome) These isoforms of PKC bind DAG and phosphatidylserine (PS), but unlike the conventional forms, do not require calcium for PS binding.
TRPC3/6/7 ProteinREACT_23108 (Reactome)

Annotated Interactions

No annotated interactions

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