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.
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
DiScipio RG, Davie EW.; ''Characterization of protein S, a gamma-carboxyglutamic acid containing protein from bovine and human plasma.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Chung SH, Polgar J, Reed GL.; ''Protein kinase C phosphorylation of syntaxin 4 in thrombin-activated human platelets.''; PubMedEurope PMCScholia
Walker TR, Watson SP.; ''Synergy between Ca2+ and protein kinase C is the major factor in determining the level of secretion from human platelets.''; PubMedEurope PMCScholia
Tao N, Wagner SJ, Lublin DM.; ''CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails.''; PubMedEurope PMCScholia
Tolmachova T, Abrink M, Futter CE, Authi KS, Seabra MC.; ''Rab27b regulates number and secretion of platelet dense granules.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Al Hawas R, Ren Q, Ye S, Karim ZA, Filipovich AH, Whiteheart SW.; ''Munc18b/STXBP2 is required for platelet secretion.''; PubMedEurope PMCScholia
Houng A, Polgar J, Reed GL.; ''Munc18-syntaxin complexes and exocytosis in human platelets.''; PubMedEurope PMCScholia
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.''; PubMedEurope PMCScholia
Ichinose A, Hendrickson LE, Fujikawa K, Davie EW.; ''Amino acid sequence of the a subunit of human factor XIII.''; PubMedEurope PMCScholia
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.
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.
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'.
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'.
After Platelet activation '78 kDa glucose-regulated protein' from the endoplasmic reticulum lumen is released in to the extracellular platelet releasate.
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.
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).
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.
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.
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.
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.
Try the New WikiPathways
View approved pathways at the new wikipathways.org.Quality Tags
Ontology Terms
Bibliography
History
External references
DataNodes
dense granule
contentdense granule
contentconventional
protein kinase Cgranule membrane components that are released on
degranulationgranule membrane components that are released on
degranulationgranule membrane
componentsgranule membrane
components(inferred)
cytosolic proteins(inferred)
cytosolic proteinssecretory granule
proteinssecretory granule
proteinsAnnotated Interactions
dense granule
contentdense granule
contentconventional
protein kinase Cconventional
protein kinase Cconventional
protein kinase Cgranule membrane components that are released on
degranulationgranule membrane components that are released on
degranulationgranule membrane
componentsgranule membrane
components(inferred)
cytosolic proteins(inferred)
cytosolic proteinssecretory granule
proteinssecretory granule
proteinsThis reaction is mediated by the 'calcium-dependent protein kinase C activity' of 'Activated Ca++ and DAG dependent PKC'.
This reaction is mediated by the 'calcium-dependent protein kinase C activity' of 'Activated Ca++ and DAG dependent PKC'.