Factors involved in megakaryocyte development and platelet production (Homo sapiens)

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1-328418143117309, 10112024, 2512, 1319232115, 16372227262932-36endosome lumennucleoplasmcytosolmitochondrial matrixREST:REST DNA binding sitesRAD51BC-terminal EH domain containing proteinsCDK2:CABLES1:Wee-1f-actinAMPHemoglobin subunit epsilon1D-myo-Inositol 1,3,4,5,6-pentakisphosphateGDPIRF2:promoters of INF alpha, INF betaMitofusinsRAC1, CDC42Interferon regulatory factor 1C-terminal EH domain containing proteins:Rabenosyn-5GTPHemoglobin subunit betaHP1alpha:Histone H3 methylated at K9ATPADPCDK5:CABLES:ABLSingle-stranded DNACDK5NF-E21D-myo-inositol 1,3,4-trisphosphateCABLESIRF1:Promotors of IFN alpha, IFN betaDOCK-GEFsRabenosyn-5SIN3ABHC complexF-actin-capping protein subunit betaBHC complex:REST:REST DNA binding sitesInositol-tetrakisphosphate 1-kinasep(Y813)-JAK2RAD51B:RAD51CJumonji domain-containing protein 1CADPSH2B family:p(Y813)-JAK2Hemoglobin subunit gamma-2Histone H3 mono or di-methylated at K9PKA tetramerLRRC16A:F-actin capping proteinTranscription factor NF-E2 45 kDa subunitCdk2Leucine-rich repeat-containing protein 16AGATA proteinsWee1RAD51CHeterochromatin protein 1 homolog alphaMitofusin complexInterferon regulatory factor 2CABLES1ABL1Promotor region of beta-globinKinesinsHemoglobin subunit gamma-1Hemoglobin subunit deltaIFN alpha/beta (IFNA/B)F-actin capping proteinRAD51B:RAD51C:Single-stranded DNAMYBRas-related protein Rab-5AVacuolar protein sorting-associated protein 45Histone H3 mono- or unmethylated at K9Promotor region of interferon betaF-actin capping protein alpha subunitRabenosyn-5:VPS-451D-myo-inositol 1,3,4,5/6-tetrakisphosphateHistone H3 methylated at lysine-9Adenylate kinase 3p53 proteinSmall Maf family membersZFPM proteins:GATA proteinsZFPM1, ZFPM2F-actin capping protein:f-actinp53:MYB:SIN3ANF-E2:Promoter region of beta-globinDual-specific AKAPs:PKA tetramer1D-myo-inositol 3,4,5,6-tetrakisphosphateDOCK-GEFs:RAC1, CDC42SH2B familyPromotor region of interferon alphaDual-specific AKAPs5-84


Description

Megakaryocytes (MKs) give rise to circulating platelets (thrombocytes) through terminal differentiation of MKs which release cytoplasmic fragments as circulating platelets. As MKs mature they undergo endoreduplication (polyploidisation) and expansion of cytoplasmic mass to cell sizes larger than 50-100 microns, and ploidy ranges up to 128 N. As MK's mature, the polyploid nucleus becomes horseshoe-shaped, the cytoplasm expands, and platelet organelles and the demarcation membrane system are amplified. Proplatelet projections form which give rise to de novo circulating platelets (Deutsch & Tomer 2006).
The processes of megakaryocytopoiesis and platelet production occur within a complex microenvironment where chemokines, cytokines and adhesive interactions play major roles (Avecilla et al. 2004). Megakaryocytopoiesis is regulated at several levels including proliferation, differentiation and platelet release (Kaushansky 2003). Thrombopoietin (TPO/c-Mpl ligand) is the most potent cytokine stimulating proliferation and maturation of MK progenitors (Kaushansky 2005) but many other growth factors are involved. MK development is controlled by the action of multiple Transcriptin Factors, many MK-specific genes are co-regulated by GATA and friend of GATA (FOG), RUNX1 and ETS proteins. Nuclear factor erythroid 2 (NF-E2) which has an MK-erythroid specific 45-kDa subunit controls terminal MK maturation, proplatelet formation and platelet release (Schulze & Shivdasani 2004). NF-E2 deficient mice have profound thrombocytopenia (Shiraga et al. 1999). c-myb functions with p300 as a negative regulator of thrombopoiesis (Metcalf et al. 2005). During MK maturation, internal membrane systems, granules and organelles are assembled. Cytoplasmic fragmentation requires changes in the MK cytoskeleton and formation of organelles and channels. Individual organelles migrate from the cell body to the proplatelet ends, with approximately 30 percent of organelles/granules in motion at any given time (Richardson et al. 2005).

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Bibliography

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History

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114719view16:20, 25 January 2021ReactomeTeamReactome version 75
113164view11:23, 2 November 2020ReactomeTeamReactome version 74
112392view15:32, 9 October 2020ReactomeTeamReactome version 73
101296view11:18, 1 November 2018ReactomeTeamreactome version 66
100833view20:49, 31 October 2018ReactomeTeamreactome version 65
100374view19:24, 31 October 2018ReactomeTeamreactome version 64
99921view16:07, 31 October 2018ReactomeTeamreactome version 63
99476view14:40, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99130view12:40, 31 October 2018ReactomeTeamreactome version 62
93897view13:43, 16 August 2017ReactomeTeamreactome version 61
93470view11:24, 9 August 2017ReactomeTeamreactome version 61
87443view13:42, 22 July 2016MkutmonOntology Term : 'hemostasis pathway' added !
86564view09:21, 11 July 2016ReactomeTeamreactome version 56
83188view10:19, 18 November 2015ReactomeTeamVersion54
81558view13:05, 21 August 2015ReactomeTeamVersion53
77027view08:32, 17 July 2014ReactomeTeamFixed remaining interactions
76732view12:09, 16 July 2014ReactomeTeamFixed remaining interactions
76057view10:12, 11 June 2014ReactomeTeamRe-fixing comment source
75767view11:27, 10 June 2014ReactomeTeamReactome 48 Update
75117view14:06, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74764view08:51, 30 April 2014ReactomeTeamReactome46
42038view21:52, 4 March 2011MaintBotAutomatic update
39841view05:52, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
1D-myo-Inositol

1,3,4,5,6- pentakisphosphate

Metabolite16322 (ChEBI)
1D-myo-inositol

1,3,4,5/6- tetrakisphosphate

MetaboliteREACT_26666 (Reactome)
1D-myo-inositol

3,4,5,6- tetrakisphosphate

Metabolite15844 (ChEBI)
1D-myo-inositol 1,3,4-

trisphosphate

Metabolite18228 (ChEBI)
ABL1 ProteinP00519 (UniProt)
ADP Metabolite16761 (ChEBI)
AMP Metabolite16027 (ChEBI)
ATP Metabolite15422 (ChEBI)
Adenylate kinase 3 ProteinQ9UIJ7 (UniProt)
BHC complex ComplexREACT_26743 (Reactome)
BHC complex:REST:

REST DNA binding sites

ComplexREACT_25596 (Reactome)
C-terminal EH

domain containing proteins

ProteinREACT_26767 (Reactome)
C-terminal EH

domain containing proteins:Rabenosyn- 5

ComplexREACT_26657 (Reactome)
CABLES ProteinREACT_26006 (Reactome)
CABLES1 ProteinQ8TDN4 (UniProt)
CDK2:CABLES1:Wee-

1

ComplexREACT_25979 (Reactome)
CDK5 ProteinQ00535 (UniProt)
CDK5:CABLES:ABL ComplexREACT_26864 (Reactome)
Cdk2 ProteinP24941 (UniProt)
DOCK-

GEFs

ProteinREACT_26129 (Reactome)
DOCK-GEFs:RAC1,

CDC42

ComplexREACT_25414 (Reactome)
Dual-specific

AKAPs

ProteinREACT_25713 (Reactome)
Dual-specific AKAPs:

PKA tetramer

ComplexREACT_25534 (Reactome)
F-actin capping

protein

ComplexREACT_26977 (Reactome)
F-actin capping

protein alpha subunit

ProteinREACT_25420 (Reactome)
F-actin capping

protein:f-actin

ComplexREACT_26552 (Reactome)
F-actin-capping

protein subunit beta

ProteinP47756 (UniProt)
GATA proteins ProteinREACT_26707 (Reactome)
GDP Metabolite17552 (ChEBI)
GTP Metabolite15996 (ChEBI)
HP1alpha:Histone H3

methylated at K9

ComplexREACT_27026 (Reactome)
Hemoglobin subunit

beta

ProteinP68871 (UniProt)
Hemoglobin subunit

delta

ProteinP02042 (UniProt)
Hemoglobin subunit

epsilon

ProteinP02100 (UniProt)
Hemoglobin subunit

gamma-1

ProteinP69891 (UniProt)
Hemoglobin subunit

gamma-2

ProteinP69892 (UniProt)
Heterochromatin

protein 1 homolog alpha

ProteinP45973 (UniProt)
Histone H3

methylated at lysine-9

ProteinREACT_25651 (Reactome)
Histone H3 mono or

di-methylated at K9

ProteinREACT_27055 (Reactome)
Histone H3 mono- or

unmethylated at K9

ProteinREACT_27021 (Reactome)
IFN alpha/beta

(IFNA/B)

ProteinREACT_26595 (Reactome)
IRF1:Promotors of

IFN alpha, IFN beta

ComplexREACT_26239 (Reactome)
IRF2:promoters of

INF alpha, INF beta

ComplexREACT_26555 (Reactome)
Inositol-

tetrakisphosphate 1- kinase

ProteinQ13572 (UniProt)
Interferon regulatory

factor 1

ProteinP10914 (UniProt)
Interferon regulatory

factor 2

ProteinP14316 (UniProt)
Jumonji domain-

containing protein 1C

ProteinQ15652 (UniProt)
Kinesins PathwayREACT_25201 (Reactome) Kinesins are a superfamily of microtubule-based motor proteins that have diverse functions in transport of vesicles, organelles and chromosomes, and regulate microtubule dynamics. There are 14 families of kinesins, all reprsented in humans. A standardized nomenclature was published in 2004 (Lawrence et al.).
LRRC16A:F-actin

capping protein

ComplexREACT_26939 (Reactome)
Leucine-rich repeat-

containing protein 16A

ProteinQ5VZK9 (UniProt)
MYB ProteinP10242 (UniProt)
Mitofusin complex ComplexREACT_25928 (Reactome)
Mitofusins ProteinREACT_26095 (Reactome)
NF-E2 ComplexREACT_26613 (Reactome)
NF-E2:Promoter

region of beta-globin

ComplexREACT_27022 (Reactome)
PKA tetramer ComplexREACT_5749 (Reactome)
Promotor region of

beta-globin

UnknownREACT_25634 (Reactome)
Promotor region of

interferon alpha

UnknownREACT_26381 (Reactome)
Promotor region of

interferon beta

UnknownREACT_25836 (Reactome)
RAC1,

CDC42

ProteinREACT_25943 (Reactome)
RAD51B ProteinO15315 (UniProt)
RAD51B:

RAD51C

ComplexREACT_26032 (Reactome)
RAD51B:RAD51C:

Single-stranded DNA

ComplexREACT_25469 (Reactome)
RAD51C ProteinO43502 (UniProt)
REST:REST DNA

binding sites

ComplexREACT_25691 (Reactome)
Rabenosyn-5 ProteinQ9H1K0 (UniProt)
Rabenosyn-5:

VPS-45

ComplexREACT_26968 (Reactome)
Ras-related protein

Rab-5A

ProteinP20339 (UniProt)
SH2B family ProteinREACT_26906 (Reactome)
SH2B family:p(Y813)-

JAK2

ComplexREACT_26825 (Reactome)
SIN3A ProteinQ96ST3 (UniProt)
Single-stranded DNA Unknown9160 (ChEBI)
Small Maf family

members

ProteinREACT_25969 (Reactome)
Transcription factor

NF-E2 45 kDa subunit

ProteinQ16621 (UniProt)
Vacuolar protein

sorting-associated protein 45

ProteinQ9NRW7 (UniProt)
Wee1 ProteinP30291 (UniProt)
ZFPM proteins:GATA

proteins

ComplexREACT_25675 (Reactome)
ZFPM1, ZFPM2 ProteinREACT_25560 (Reactome)
f-actin UnknownREACT_25435 (Reactome)
p(Y813)-

JAK2

ProteinO60674 (UniProt)
p53 protein ProteinP04637 (UniProt)
p53:MYB:SIN3A ComplexREACT_26185 (Reactome)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1815"
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