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Factors involved in megakaryocyte development and platelet production
Stable Identifier
R-HSA-983231
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Hemostasis (Homo sapiens)
Factors involved in megakaryocyte development and platelet production (Homo sapiens)
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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 MKs 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 transcription 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). MYB (c-myb) functions with EP300 (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).
Literature References
PubMed ID
Title
Journal
Year
16856888
Megakaryocyte development and platelet production
Tomer, A
,
Deutsch, VR
Br J Haematol
2006
17934486
Transcriptional control of megakaryocyte development
Goldfarb, AN
Oncogene
2007
17635743
From hematopoietic stem cells to platelets
Bluteau, D
,
Chang, Y
,
Vainchenker, W
,
Debili, N
J Thromb Haemost
2007
Participants
Events
RAD51B binds RAD51C
(Homo sapiens)
RAD51B:RAD51C binds single-stranded DNA
(Homo sapiens)
Dual-specific AKAPs bind type I and II PKA regulatory subunits
(Homo sapiens)
Mitofusins trans-interact linking mitochondria prior to fusion
(Homo sapiens)
p53, SIN3A and MYB form a complex
(Homo sapiens)
IRF1 binds the promoters of Interferon alpha and beta
(Homo sapiens)
Expression of Interferon-alpha and beta
(Homo sapiens)
IRF2 binds the promoters of Interferon alpha and beta
(Homo sapiens)
HP1 alpha binds Histone H3K9(me)3
(Homo sapiens)
ITPK1 converts Ins-3,4,5,6-P4 to Ins-1,3,4,5,6-P5
(Homo sapiens)
ITPK1 converts Ins-1,3,4-P3 to Ins-1,3,4,5-P4
(Homo sapiens)
ITPK1 converts Ins-1,3,4-P3 to Ins-1,3,4,6-P4
(Homo sapiens)
LRRC16A binds F-actin capping protein
(Homo sapiens)
F-actin capping protein is a heterodimer
(Homo sapiens)
F-actin capping protein binds to the barbed end of elongating F-actin
(Homo sapiens)
MICAL1 produces NADP+, H2O2
(Homo sapiens)
REST recruits the BHC complex
(Homo sapiens)
ZFPM proteins bind GATA proteins
(Homo sapiens)
JMJD1C demethylates H3K9 mono- and di-methylation
(Homo sapiens)
SH2B proteins bind JAK2
(Homo sapiens)
Adenylate Kinase 3 is a GTP-AMP phosphotransferase
(Homo sapiens)
NFE2 is a heterodimer
(Homo sapiens)
NFE2 binds the beta globin locus control region
(Homo sapiens)
Expression of globin genes under control of the beta globin control region
(Homo sapiens)
EHD proteins interact with Rabenosyn-5
(Homo sapiens)
Rabenosyn-5 connects Rab5 to VPS-45
(Homo sapiens)
DOCKs bind to RhoGEFs
(Homo sapiens)
Cables link CDK5 and ABL1
(Homo sapiens)
Cables1 links CDK2 and WEE1
(Homo sapiens)
Kinesins
(Homo sapiens)
Participates
as an event of
Hemostasis (Homo sapiens)
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Authored
Akkerman, JW (2010-10-29)
Reviewed
Ouwehand, WH (2010-11-12)
Created
Jupe, S (2010-10-29)
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