Response to elevated platelet cytosolic Ca ions (Homo sapiens)

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872, 7457552516391platelet dense granule lumenplatelet alpha granule lumenlysosomal lumenstored secretory granuleendoplasmic reticulum lumencytosolPlatelet dense granule content78 kDa glucose-regulated proteinADPPhosphorylated syntaxin 4Platelet alpha granule membrane components that are released on degranulationPlatelet releasate secretory granule proteinsPlatelet SEC1 protein78 kDa glucose-regulated proteinATPPlatelet alpha granule contentsGAS6Activated conventional protein kinase CGAS61,2-DiacylglycerolCalumeninPlatelet alpha granule membrane components that are released on degranulationPlatelet releasate (inferred) cytosolic proteinsProactivator polypeptideProtein Kinase C, conventionalCalciumABCC4 transported dense granule contentPlatelet dense granule contentPhosphatidylserineSyntaxin 4Proactivator polypeptideABCC4 transported dense granule contentPlatelet releasate cytosolic proteinsPlatelet releasate secretory granule proteinsPlatelet dense granule membrane componentsPlatelet dense granule membrane componentsCalumeninPlatelet releasate cytosolic proteinsPlatelet releasate (inferred) cytosolic proteinsPlatelet alpha granule contentsPhosphorylated platelet SEC1 proteinABCC455


Description

Activation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium and activation of Protein Kinase C (PKC). Phospholipase C cleaves the phosphodiester bond in PIP2 to form 1,2 Diacylglycerol (DAG) and 1,4,5-inositol trisphosphate (IP3). IP3 opens Ca2+ channels in the platelet dense tubular system, raising intracellular Ca2+ levels. DAG is a second messenger that regulates a family of Ser/Thr kinases consisting of PKC isozymes (Nishizuka 1995). DAG achieves activation of PKC isozymes by increasing their affinity for phospholipid. Most PKC enzymes are also calcium-dependent, so their activation is in synergy with the rise in intracellular Ca2+. Platelets contain several PKC isoforms that can be activated by DAG and/or Ca2+ (Chang 1997).

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Bibliography

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  1. Oancea E, Meyer T.; ''Protein kinase C as a molecular machine for decoding calcium and diacylglycerol signals.''; PubMed Europe PMC Scholia
  2. Harrison P, Cramer EM.; ''Platelet alpha-granules.''; PubMed Europe PMC Scholia
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  4. Ross D, Joyner WL.; ''Resting distribution and stimulated translocation of protein kinase C isoforms alpha, epsilon and zeta in response to bradykinin and TNF in human endothelial cells.''; PubMed Europe PMC Scholia
  5. DiScipio RG, Davie EW.; ''Characterization of protein S, a gamma-carboxyglutamic acid containing protein from bovine and human plasma.''; PubMed Europe PMC Scholia
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  7. Reed GL, Houng AK, Fitzgerald ML.; ''Human platelets contain SNARE proteins and a Sec1p homologue that interacts with syntaxin 4 and is phosphorylated after thrombin activation: implications for platelet secretion.''; PubMed Europe PMC Scholia
  8. Iwamoto R, Higashiyama S, Mitamura T, Taniguchi N, Klagsbrun M, Mekada E.; ''Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity.''; PubMed Europe PMC Scholia
  9. Chung SH, Polgar J, Reed GL.; ''Protein kinase C phosphorylation of syntaxin 4 in thrombin-activated human platelets.''; PubMed Europe PMC Scholia
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  17. Gogstad GO, Hagen I, Korsmo R, Solum NO.; ''Characterization of the proteins of isolated human platelet alpha-granules. Evidence for a separate alpha-granule-pool of the glycoproteins IIb and IIIa.''; PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
123617view08:20, 7 August 2022EgonwModified title
114827view16:32, 25 January 2021ReactomeTeamReactome version 75
113273view11:34, 2 November 2020ReactomeTeamReactome version 74
112485view15:44, 9 October 2020ReactomeTeamReactome version 73
101397view11:28, 1 November 2018ReactomeTeamreactome version 66
100935view21:04, 31 October 2018ReactomeTeamreactome version 65
100472view19:38, 31 October 2018ReactomeTeamreactome version 64
100017view16:21, 31 October 2018ReactomeTeamreactome version 63
99570view14:54, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99193view12:43, 31 October 2018ReactomeTeamreactome version 62
93756view13:34, 16 August 2017ReactomeTeamreactome version 61
93276view11:19, 9 August 2017ReactomeTeamreactome version 61
86355view09:16, 11 July 2016ReactomeTeamreactome version 56
85040view08:26, 10 April 2016EgonwThis is even more accurate.
84779view09:41, 20 March 2016EgonwFixed the ChEBI IDs (removed the R-HSA prefix).
83141view10:08, 18 November 2015ReactomeTeamVersion54
81485view13:01, 21 August 2015ReactomeTeamVersion53
76962view08:24, 17 July 2014ReactomeTeamFixed remaining interactions
76667view12:03, 16 July 2014ReactomeTeamFixed remaining interactions
75996view10:05, 11 June 2014ReactomeTeamRe-fixing comment source
75699view11:03, 10 June 2014ReactomeTeamReactome 48 Update
75055view13:56, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74699view08:46, 30 April 2014ReactomeTeamReactome46
68987view17:43, 8 July 2013MaintBotUpdated to 2013 gpml schema
45238view18:17, 7 October 2011KhanspersOntology Term : 'phosphatidylinositol 3-kinase signaling pathway' added !
45046view19:05, 6 October 2011ThomasOntology Term : 'platelet' added !
42119view21:58, 4 March 2011MaintBotAutomatic update
39929view05:56, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
1,2-Diacylglycerol 17815 (ChEBI)
78 kDa glucose-

regulated protein

ProteinP11021 (UniProt)
ABCC4 ProteinO15439 (UniProt)
ABCC4 transported

dense granule content

MetaboliteREACT_24476 (Reactome)
ABCC4 transported

dense granule content

MetaboliteREACT_24718 (Reactome)
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Activated conventional

protein kinase C

ComplexREACT_4434 (Reactome)
Calcium Metabolite29108 (ChEBI)
Calumenin ProteinO43852 (UniProt)
GAS6 ProteinQ14393 (UniProt)
Phosphatidylserine 18304 (ChEBI)
Phosphorylated

platelet SEC1 protein

ProteinO00186 (UniProt)
Phosphorylated

syntaxin 4

ProteinQ12846 (UniProt)
Platelet SEC1 protein ProteinO00186 (UniProt)
Platelet alpha granule

contents

ProteinREACT_21970 (Reactome)
Platelet alpha granule

contents

ProteinREACT_22076 (Reactome)
Platelet alpha granule

membrane components that are released on degranulation

ProteinREACT_25913 (Reactome)
Platelet alpha granule

membrane components that are released on degranulation

ProteinREACT_26523 (Reactome)
Platelet dense

granule content

REACT_21516 (Reactome)
Platelet dense

granule content

MetaboliteREACT_21949 (Reactome)
Platelet dense

granule membrane components

ProteinREACT_21483 (Reactome)
Platelet dense

granule membrane components

ProteinREACT_22010 (Reactome)
Platelet releasate

(inferred) cytosolic proteins

ProteinREACT_21475 (Reactome)
Platelet releasate

(inferred) cytosolic proteins

ProteinREACT_21781 (Reactome)
Platelet releasate

cytosolic proteins

ProteinREACT_21985 (Reactome)
Platelet releasate

cytosolic proteins

ProteinREACT_21997 (Reactome)
Platelet releasate

secretory granule proteins

ProteinREACT_21832 (Reactome)
Platelet releasate

secretory granule proteins

ProteinREACT_21850 (Reactome)
Proactivator

polypeptide

ProteinP07602 (UniProt)
Protein Kinase C,

conventional

ProteinREACT_4876 (Reactome) These PKC isoforms are activated by PS in a Ca2+-dependent manner; they also bind DAG, which both increases the specificity of the enzyme for PS and also shifts the affinity for Ca2+ into the physiological range. They are targets of the tumour-promoting phorbol ester PMA, which activates these enzymes by eliminating the requirement for DAG and decreasing the concentration of Ca2+ needed for activation.
Syntaxin 4 ProteinQ12846 (UniProt)

Annotated Interactions

No annotated interactions

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