Response to elevated platelet cytosolic Ca ions (Homo sapiens)
From WikiPathways
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).
View original pathway at:Reactome.
Quality Tags
Ontology Terms
Saving...Bibliography
View all... |
- Oancea E, Meyer T.; ''Protein kinase C as a molecular machine for decoding calcium and diacylglycerol signals.''; PubMed Europe PMC Scholia
- Harrison P, Cramer EM.; ''Platelet alpha-granules.''; PubMed Europe PMC Scholia
- Coppinger JA, Cagney G, Toomey S, Kislinger T, Belton O, McRedmond JP, Cahill DJ, Emili A, Fitzgerald DJ, Maguire PB.; ''Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions.''; PubMed Europe PMC Scholia
- 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
- DiScipio RG, Davie EW.; ''Characterization of protein S, a gamma-carboxyglutamic acid containing protein from bovine and human plasma.''; PubMed Europe PMC Scholia
- Jedlitschky G, Tirschmann K, Lubenow LE, Nieuwenhuis HK, Akkerman JW, Greinacher A, Kroemer HK.; ''The nucleotide transporter MRP4 (ABCC4) is highly expressed in human platelets and present in dense granules, indicating a role in mediator storage.''; PubMed Europe PMC Scholia
- 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
- 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
- Chung SH, Polgar J, Reed GL.; ''Protein kinase C phosphorylation of syntaxin 4 in thrombin-activated human platelets.''; PubMed Europe PMC Scholia
- Fukami MH.; ''Isolation of dense granules from human platelets.''; PubMed Europe PMC Scholia
- Walker TR, Watson SP.; ''Synergy between Ca2+ and protein kinase C is the major factor in determining the level of secretion from human platelets.''; PubMed Europe PMC Scholia
- Tao N, Wagner SJ, Lublin DM.; ''CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails.''; PubMed Europe PMC Scholia
- Tolmachova T, Abrink M, Futter CE, Authi KS, Seabra MC.; ''Rab27b regulates number and secretion of platelet dense granules.''; PubMed Europe PMC Scholia
- Wijten P, van Holten T, Woo LL, Bleijerveld OB, Roest M, Heck AJ, Scholten A.; ''High precision platelet releasate definition by quantitative reversed protein profiling--brief report.''; PubMed Europe PMC Scholia
- Al Hawas R, Ren Q, Ye S, Karim ZA, Filipovich AH, Whiteheart SW.; ''Munc18b/STXBP2 is required for platelet secretion.''; PubMed Europe PMC Scholia
- Houng A, Polgar J, Reed GL.; ''Munc18-syntaxin complexes and exocytosis in human platelets.''; PubMed Europe PMC Scholia
- 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
- Ichinose A, Hendrickson LE, Fujikawa K, Davie EW.; ''Amino acid sequence of the a subunit of human factor XIII.''; PubMed Europe PMC Scholia
History
View all... |
External references
DataNodes
| View all... |
| Name | Type | Database reference | Comment |
|---|---|---|---|
| 5HT | Metabolite | CHEBI:28790 (ChEBI)  | |
| ABCC4 transported
dense granule content | Metabolite | R-ALL-429153 (Reactome) | |
| ABCC4 transported
dense granule content | Metabolite | R-ALL-429160 (Reactome) | |
| ABCC4 | Protein | O15439 (Uniprot-TrEMBL) | |
| ADP | Metabolite | CHEBI:16761 (ChEBI) | |
| ADP | Metabolite | CHEBI:16761 (ChEBI) | |
| ATP | Metabolite | CHEBI:15422 (ChEBI) | |
| ATP | Metabolite | CHEBI:15422 (ChEBI) | |
| Activated
conventional protein kinase C | Complex | R-HSA-139830 (Reactome) | |
| CALU | Protein | O43852 (Uniprot-TrEMBL) | |
| Ca2+ | Metabolite | CHEBI:29108 (ChEBI) | |
| Ca2+ | Metabolite | CHEBI:29108 (ChEBI) | |
| DAG | Metabolite | CHEBI:17815 (ChEBI) | |
| DAG | Complex | R-HSA-CHEBI:17815 (Reactome) | |
| GDP | Metabolite | CHEBI:17552 (ChEBI) | |
| GTP | Metabolite | CHEBI:15996 (ChEBI) | |
| HSPA5 | Protein | P11021 (Uniprot-TrEMBL) | |
| Mg2+ | Metabolite | CHEBI:18420 (ChEBI) | |
| PPi | Metabolite | CHEBI:29888 (ChEBI) | |
| PSAP(60-142) | Protein | P07602 (Uniprot-TrEMBL) | |
| Phosphatidylserine | Metabolite | CHEBI:18303 (ChEBI) | |
| Phosphatidylserine | Complex | R-HSA-CHEBI:18303 (Reactome) | |
| Pi | Metabolite | CHEBI:18367 (ChEBI) | |
| Platelet alpha granule contents | Protein | R-HSA-481003 (Reactome) | |
| Platelet alpha granule contents | Protein | R-HSA-481033 (Reactome) | |
| Platelet alpha
granule membrane components that are released on degranulation | Protein | R-HSA-964721 (Reactome) | |
| Platelet alpha
granule membrane components that are released on degranulation | Protein | R-HSA-964722 (Reactome) | |
| Platelet dense granule content | Metabolite | R-ALL-481002 (Reactome) | |
| Platelet dense granule content | Complex | R-HSA-R-ALL-481030 (Reactome) | |
| Platelet dense
granule membrane components | Protein | R-HSA-481004 (Reactome) | |
| Platelet dense
granule membrane components | Protein | R-HSA-481006 (Reactome) | |
| Platelet releasate
(inferred) cytosolic proteins | Protein | R-HSA-482764 (Reactome) | |
| Platelet releasate
(inferred) cytosolic proteins | Protein | R-HSA-482774 (Reactome) | |
| Platelet releasate cytosolic proteins | Protein | R-HSA-482768 (Reactome) | |
| Platelet releasate cytosolic proteins | Protein | R-HSA-482771 (Reactome) | |
| Platelet releasate
secretory granule proteins | Protein | R-HSA-482765 (Reactome) | |
| Platelet releasate
secretory granule proteins | Protein | R-HSA-482769 (Reactome) | |
| Protein Kinase C, conventional | Protein | R-HSA-114528 (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. |
| STX4 | Protein | Q12846 (Uniprot-TrEMBL) | |
| STXBP3 | Protein | O00186 (Uniprot-TrEMBL) | |
| p-STXBP3 | Protein | O00186 (Uniprot-TrEMBL) |
Annotated Interactions
| View all... |
| Source | Target | Type | Database reference | Comment |
|---|---|---|---|---|
| ABCC4 transported
dense granule content | Arrow | R-HSA-429157 (Reactome) | ||
| ABCC4 transported
dense granule content | R-HSA-429157 (Reactome) | |||
| ABCC4 | mim-catalysis | R-HSA-429157 (Reactome) | ||
| ADP | Arrow | R-HSA-114683 (Reactome) | ||
| ADP | Arrow | R-HSA-114684 (Reactome) | ||
| ATP | R-HSA-114683 (Reactome) | |||
| ATP | R-HSA-114684 (Reactome) | |||
| Activated
conventional protein kinase C | Arrow | R-HSA-114553 (Reactome) | ||
| Activated
conventional protein kinase C | mim-catalysis | R-HSA-114683 (Reactome) | ||
| Activated
conventional protein kinase C | mim-catalysis | R-HSA-114684 (Reactome) | ||
| CALU | Arrow | R-HSA-350745 (Reactome) | ||
| CALU | R-HSA-350745 (Reactome) | |||
| Ca2+ | R-HSA-114553 (Reactome) | |||
| DAG | Arrow | R-HSA-114553 (Reactome) | ||
| DAG | R-HSA-114553 (Reactome) | |||
| HSPA5 | Arrow | R-HSA-351323 (Reactome) | ||
| HSPA5 | R-HSA-351323 (Reactome) | |||
| PSAP(60-142) | Arrow | R-HSA-351341 (Reactome) | ||
| PSAP(60-142) | R-HSA-351341 (Reactome) | |||
| Phosphatidylserine | R-HSA-114553 (Reactome) | |||
| Platelet alpha granule contents | Arrow | R-HSA-481007 (Reactome) | ||
| Platelet alpha granule contents | R-HSA-481007 (Reactome) | |||
| Platelet alpha
granule membrane components that are released on degranulation | Arrow | R-HSA-481044 (Reactome) | ||
| Platelet alpha
granule membrane components that are released on degranulation | R-HSA-481044 (Reactome) | |||
| Platelet dense granule content | Arrow | R-HSA-481009 (Reactome) | ||
| Platelet dense granule content | R-HSA-481009 (Reactome) | |||
| Platelet dense
granule membrane components | Arrow | R-HSA-481010 (Reactome) | ||
| Platelet dense
granule membrane components | R-HSA-481010 (Reactome) | |||
| Platelet releasate
(inferred) cytosolic proteins | Arrow | R-HSA-482775 (Reactome) | ||
| Platelet releasate
(inferred) cytosolic proteins | R-HSA-482775 (Reactome) | |||
| Platelet releasate cytosolic proteins | Arrow | R-HSA-482772 (Reactome) | ||
| Platelet releasate cytosolic proteins | R-HSA-482772 (Reactome) | |||
| Platelet releasate
secretory granule proteins | Arrow | R-HSA-482770 (Reactome) | ||
| Platelet releasate
secretory granule proteins | R-HSA-482770 (Reactome) | |||
| Protein Kinase C, conventional | R-HSA-114553 (Reactome) | |||
| R-HSA-114553 (Reactome) | The conventional Protein Kinase C (cPKC) isoforms have two membrane-targetting domains, a C1 domain which binds to the membrane lipid diacylglycerol (DAG) and a C2 domain which binds membrane phospholipids such as phosphatidylserine, in a calcium-dependent manner. Association of both domains with the plasma membrane produces a conformational change that releases an autoinhibitory pseudosubstrate segment from the substrate-binding cavity, allowing substrate binding and downstream signaling. | |||
| R-HSA-114683 (Reactome) | At the beginning of this reaction, 1 molecule of 'ATP', and 1 molecule of 'Platelet SEC1 protein' are present. At the end of this reaction, 1 molecule of 'Phosphorylated platelet SEC1 protein', and 1 molecule of 'ADP' are present. This reaction is mediated by the 'calcium-dependent protein kinase C activity' of 'Activated Ca++ and DAG dependent PKC'. | |||
| R-HSA-114684 (Reactome) | At the beginning of this reaction, 1 molecule of 'ATP', and 1 molecule of 'Syntaxin 4' are present. At the end of this reaction, 1 molecule of 'Phosphorylated syntaxin 4', and 1 molecule of 'ADP' are present. This reaction is mediated by the 'calcium-dependent protein kinase C activity' of 'Activated Ca++ and DAG dependent PKC'. | |||
| R-HSA-350745 (Reactome) | After Platelet activation 'Calumenin' from the endoplasmic reticulum lumen is released in to the extracellular platelet releasate. | |||
| R-HSA-351323 (Reactome) | After Platelet activation '78 kDa glucose-regulated protein' from the endoplasmic reticulum lumen is released in to the extracellular platelet releasate. | |||
| R-HSA-351341 (Reactome) | After Platelet activation 'Proactivator polypeptide' from the lysosomal lumen is released in to the extracellular platelet releasate. | |||
| R-HSA-429157 (Reactome) | ABCC4 (Multidrug resistance protein 4 /MOAT-B) is a member of the MRP/ABCC subfamily of ATP-binding cassette transporters, capable of pumping a wide variety of endogenous and xenobiotic anionic compounds out of the cell. ABCC4 also transports molecules involved in cellular signalling, including cyclic nucleotides, eicosanoids, urate and conjugated steroids. ABCC4 has a dual localisation in polarised cells that suggests a key function in cellular protection and extracellular signalling pathways. It is also highly expressed on platelet dense granule membranes where it is believed to contribute to the accumulation of dense granule content. | |||
| R-HSA-481007 (Reactome) | Alpha granules contain mainly polypeptides such as fibrinogen, von Willebrand factor, growth factors and protease inhibitors that supplement thrombin generation at the site of injury. In addtion to their role in hemostasis, platelets also contain angiogenesis stimulators and inhibitors (Italiano et al. 2008). | |||
| R-HSA-481009 (Reactome) | ADP is the most important constituent of dense granules, essential for recruiting platelets to the site of vascular injury. Other components include ATP, Ca++, GDP, GTP, Mg++, orthophospate, pyrophosphate, and serotonin. | |||
| R-HSA-481010 (Reactome) | Constituents of the platelet dense granule membrane are incorporated into the platelet membrane following exocytosis of granule content. | |||
| R-HSA-481044 (Reactome) | Constituents of the platelet alpha granule membrane are incorporated into the platelet membrane following exocytosis of granule content. | |||
| R-HSA-482770 (Reactome) | Platelet releasate contains a range of proteins that do not originate in specialized storage granules. In some cases platelet lysis may contribute to the presence of these proteins in the platelet relesate. | |||
| R-HSA-482772 (Reactome) | Platelet releasate contains a range of proteins that do not originate in specialized storage granules. In some cases platelet lysis may contribute to the presence of these proteins in the platelet relesate. | |||
| R-HSA-482775 (Reactome) | Platelet releasate contains a range of proteins that do not originate in specialized storage granules. In some cases platelet lysis may contribute to the presence of these proteins in the platelet relesate. | |||
| STX4 | Arrow | R-HSA-114684 (Reactome) | ||
| STX4 | R-HSA-114684 (Reactome) | |||
| STXBP3 | R-HSA-114683 (Reactome) | |||
| p-STXBP3 | Arrow | R-HSA-114683 (Reactome) |
