Thrombopoietin

Revision as of 15:32, 6 September 2012 by WikiBot (talk | contribs) (Robot: Automated text replacement (-{{reflist}} +{{reflist|2}}, -<references /> +{{reflist|2}}, -{{WikiDoc Cardiology Network Infobox}} +))
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Jump to navigation Jump to search


Thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)
File:PBB Protein THPO image.jpg
PDB rendering based on 1v7m.
Available structures
PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB
Identifiers
Symbols THPO ; MGC163194; MGDF; MKCSF; ML; MPLLG; TPO
External IDs Template:OMIM5 Template:MGI HomoloGene: 398
RNA expression pattern
File:PBB GE THPO 211155 s at tn.png
File:PBB GE THPO 211154 at tn.png
File:PBB GE THPO 211831 s at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species Human Mouse
Entrez n/a n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

Thrombopoietin (leukemia virus oncogene ligand, megakaryocyte growth and development factor), also known as THPO, is a glycoprotein hormone produced mainly by the liver and the kidney that regulates the production of platelets by the bone marrow. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that fragment into large numbers of platelets.[1]

Megakaryocytopoiesis is the cellular development process that leads to platelet production. The protein encoded by this gene is a humoral growth factor that is necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. This protein is the ligand for MLP/C_MPL, the product of myeloproliferative leukemia virus oncogene.[2]

Genetics

The thrombopoietin gene is located on the long arm of chromosome 3 (q26.3-27). Abnormalities in this gene occur in some hereditary forms of thrombocytosis (high platelet count) and in some cases of leukemia. Thrombopoietin shares its first 153 amino acids with erythropoietin.[3]

Function and regulation

In the liver it is produced by parenchymal cells and sinusoidal endothelial cells. In the kidney it is made by proximal convoluted tubule cells. Along with these it is made by striated muscle and stromal cells in the bone marrow.[1] In the liver, its production is augmented by interleukin 6 (IL-6).[1]

Thrombopoietin regulates the differentiation of megakaryocytes and platelets, but studies on the removal of the thrombopoeitin receptor show that its effects on hematopoiesis are more versatile[1].

Its negative feedback is different from most hormones in endocrinology: the effector regulates the hormone directly. Thrombopoeitin is bound to the surface of platelets by the mpl receptor (CD 110) and destroyed, thereby reducing megakaryocyte exposure to the hormone.[1]

Therapeutic use

Despite numerous trials, thrombopoeitin is not used therapeutically. Theoretical uses include the procurement of platelets for donation[4], recovery of platelet counts after myelosuppressive chemotherapy.[1]

A modified recombinant form, termed "megakaryocyte growth and differentiation factor" (MGDF), caused a paradoxical reaction, delaying the development of therapeutic thrombopoietin. A quadrivalent peptide analogue is undergoing development, as well as several small molecule agents,[1] including several non-peptide ligands of c-Mpl, which act as thrombopoietin analogues.[5][6]

History

Thrombopoietin was cloned by five independent groups in 1994. Before its identification, its function has been hypothesized for as much as 30 years as being linked to the cell surface receptor c-Mpl, and in older publications thrombopoietin is described as c-Mpl ligand (the agent that binds to the c-Mpl molecule). Thrombopoietin is one of the Class I hematopoietic cytokines.[1]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Kaushansky K (2006). "Lineage-specific hematopoietic growth factors". N. Engl. J. Med. 354 (19): 2034–45. doi:10.1056/NEJMra052706. PMID 16687716.
  2. ↑ "Entrez Gene: THPO thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)".
  3. ↑ Online Mendelian Inheritance in Man (OMIM) 600044
  4. ↑ Kuter DJ, Goodnough LT, Romo J; et al. (2001). "Thrombopoietin therapy increases platelet yields in healthy platelet donors". Blood. 98 (5): 1339–45. doi:10.1182/blood.V98.5.1339. PMID 11520780.
  5. ↑ Nakamura T, Miyakawa Y, Miyamura A; et al. (2006). "A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis". Blood. 107 (11): 4300–7. doi:10.1182/blood-2005-11-4433. PMID 16484588.
  6. ↑ Jenkins JM, Williams D, Deng Y; et al. (2007). "Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist". Blood. 109 (11): 4739–41. doi:10.1182/blood-2006-11-057968. PMID 17327409.

Further reading

  • Kato T, Matsumoto A, Ogami K; et al. (1999). "Native thrombopoietin: structure and function". Stem Cells. 16 (5): 322–8. PMID 9766811.
  • Kato T (2000). "Protein characteristics of thrombopoietin". Stem Cells. 14 Suppl 1: 139–47. PMID 11012214.
  • Geddis AE, Linden HM, Kaushansky K (2002). "Thrombopoietin: a pan-hematopoietic cytokine". Cytokine Growth Factor Rev. 13 (1): 61–73. doi:10.1016/S1359-6101(01)00030-2. PMID 11750880.
  • von dem Borne A, Folman C, van den Oudenrijn S; et al. (2002). "The potential role of thrombopoietin in idiopathic thrombocytopenic purpura". Blood Rev. 16 (1): 57–9. doi:10.1054/blre.2001.0184. PMID 11913997.
  • Kaushansky K (2003). "Thrombopoietin: from theory to reality". Int. J. Hematol. 76 Suppl 1: 343–5. PMID 12430879.
  • Kralovics R, Skoda RC (2005). "Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders". Blood Rev. 19 (1): 1–13. doi:10.1016/j.blre.2004.02.002. PMID 15572213.
  • Migliaccio AR, Rana RA, Vannucchi AM, Manzoli FA (2007). "Role of thrombopoietin in mast cell differentiation". Ann. N. Y. Acad. Sci. 1106: 152–74. doi:10.1196/annals.1392.024. PMID 17468237.
  • Foster DC, Sprecher CA, Grant FJ; et al. (1995). "Human thrombopoietin: gene structure, cDNA sequence, expression, and chromosomal localization". Proc. Natl. Acad. Sci. U.S.A. 91 (26): 13023–7. PMID 7809166.
  • Chang MS, McNinch J, Basu R; et al. (1995). "Cloning and characterization of the human megakaryocyte growth and development factor (MGDF) gene". J. Biol. Chem. 270 (2): 511–4. PMID 7822271.
  • Gurney AL, Kuang WJ, Xie MH; et al. (1995). "Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin". Blood. 85 (4): 981–8. PMID 7849319.
  • Sohma Y, Akahori H, Seki N; et al. (1994). "Molecular cloning and chromosomal localization of the human thrombopoietin gene". FEBS Lett. 353 (1): 57–61. doi:10.1016/0014-5793(94)01008-0. PMID 7926023.
  • Bartley TD, Bogenberger J, Hunt P; et al. (1994). "Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl". Cell. 77 (7): 1117–24. doi:10.1016/0092-8674(94)90450-2. PMID 8020099.
  • de Sauvage FJ, Hass PE, Spencer SD; et al. (1994). "Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand". Nature. 369 (6481): 533–8. doi:10.1038/369533a0. PMID 8202154.
  • Kaushansky K, Lok S, Holly RD; et al. (1994). "Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin". Nature. 369 (6481): 568–71. doi:10.1038/369568a0. PMID 8202159.
  • Wendling F, Maraskovsky E, Debili N; et al. (1994). "cMpl ligand is a humoral regulator of megakaryocytopoiesis". Nature. 369 (6481): 571–4. doi:10.1038/369571a0. PMID 8202160.
  • Kato T, Ogami K, Shimada Y; et al. (1996). "Purification and characterization of thrombopoietin". J. Biochem. 118 (1): 229–36. PMID 8537317.
  • Hoffman RC, Andersen H, Walker K; et al. (1997). "Peptide, disulfide, and glycosylation mapping of recombinant human thrombopoietin from ser1 to Arg246". Biochemistry. 35 (47): 14849–61. doi:10.1021/bi961075b. PMID 8942648.
  • Wiestner A, Schlemper RJ, van der Maas AP, Skoda RC (1998). "An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia". Nat. Genet. 18 (1): 49–52. doi:10.1038/ng0198-49. PMID 9425899.
  • Kondo T, Okabe M, Sanada M; et al. (1998). "Familial essential thrombocythemia associated with one-base deletion in the 5'-untranslated region of the thrombopoietin gene". Blood. 92 (4): 1091–6. PMID 9694695.


External links

de:Thrombopoetin dv:ތްރޮމްބޯ ޕޮއިއިޓިން lt:Trombopoetinas Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Thrombopoietin&oldid=727306"