同: thrombopoietin receptors

WordNet

a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

PrepTutorEJDIC

=sense organ / 受信装置

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/31 21:12:44」(JST)

wiki en

The thrombopoietin receptor also known as the myeloproliferative leukemia protein or CD110 (Cluster of Differentiation 110) is a protein that in humans is encoded by the MPL (myeloproliferative leukemia virus) oncogene.^[1]

Discovery

In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferative leukemia virus that was capable of immortalizing bone marrow hematopoietic cells from different lineages. In 1992 the human homologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presence of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation.

Function

The ligand for c-mpl, thrombopoietin, was cloned in 1994. Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation.

The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs . TPO-R deficient mice were severely thrombocytopenic, emphasizing the important role of CD110 and thrombopoietin in megakaryocyte and platelet formation. Upon binding of thrombopoietin, CD110 is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated.^[1]

Interactions

Myeloproliferative leukemia virus oncogene has been shown to interact with:

ATXN2L^[2]
JAK2^[3]
thrombopoietin^[4]

Clinical relevance

Mutations in this gene have been shown to cause familial aplastic anemia.^[5]

Mutations to this gene are also associated with myelofibrosis and essential thrombocythemia.^[6] In essential thrombocythemia, mutations occur at position 505 or 515. In myelofibrosis, a mutation occurs at position 515 (W515 mutation). These mutations lead to the production of thrombopoietin receptors that are constitutively activated, or constantly turned on, which results in the overproduction of abnormal megakaryocytes.^[7]

References

^ ^a ^b "Entrez Gene: MPL myeloproliferative leukemia virus oncogene".
^ Meunier C, Bordereaux D, Porteu F, Gisselbrecht S, Chrétien S, Courtois G (Mar 2002). "Cloning and characterization of a family of proteins associated with Mpl". J. Biol. Chem. 277 (11): 9139–47. doi:10.1074/jbc.M105970200. PMID 11784712.
^ Bellido M, Te Boekhorst PA (2012). "JAK2 Inhibition: Reviewing a New Therapeutical Option in Myeloproliferative Neoplasms.". Adv Hematol 2012: 535709. doi:10.1155/2012/535709. PMID 22400031.
^ Nakaya Y, Shide K, Niwa T, Homan J, Sugahara S, Horio T, Kuramoto K, Kotera T, Shibayama H, Hori K, Naito H, Shimoda K (2011). "Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms.". Blood Cancer J 1 (7): e29. doi:10.1038/bcj.2011.29. PMID 22829185.
^ Walne AJ, Dokal A, Plagnol V, Beswick R, Kirwan M, de la Fuente J, Vulliamy T, Dokal I (December 2011). "Exome sequencing identifies MPL as a causative gene in familial aplastic anemia". Haematologica 97 (4): 524–8. doi:10.3324/haematol.2011.052787. PMC 3347658. PMID 22180433.
^ Tefferi, A; Lasho, T L; Finke, C M; Knudson, R A; Ketterling, R; Hanson, C H; Maffioli, M; Caramazza, D; Passamonti, F; Pardanani, A (2014). "CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons". Leukemia 28 (7): 1472–1477. doi:10.1038/leu.2014.3. ISSN 0887-6924.
^ Tefferi, A (2010). "Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1". Leukemia 24 (6): 1128–1138. doi:10.1038/leu.2010.69. ISSN 0887-6924.

External links

MPL protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. トロンボポエチンの生物学および生理学 biology and physiology of thrombopoietin
2. 血小板増加症患者に対するアプローチ approach to the patient with thrombocytosis
3. 血小板産生因子の臨床応用 clinical applications of thrombopoietic growth factors
4. 再生不良性貧血：病因、臨床症状および診断 aplastic anemia pathogenesis clinical manifestations and diagnosis
5. 原発性骨髄線維症における病態 pathogenetic mechanisms in primary myelofibrosis

English Journal

Positioning new treatments in the management of immune thrombocytopenia.

Arnold DM.SourceDepartment of Medicine, McMaster University, Hamilton, Ontario, Canada; Canadian Blood Services, Hamilton, Ontario, Canada. arnold@mcmaster.ca.
Pediatric blood & cancer.Pediatr Blood Cancer.2013;60 Suppl 1:S19-22. doi: 10.1002/pbc.24341. Epub 2012 Oct 25.
Immune thrombocytopenia (ITP) is a syndrome characterized by low platelet counts and an increased risk of bleeding. For most children, ITP is a self-limiting disease; however, for some children and most adults, thrombocytopenia can become chronic. Newer therapies for ITP include rituximab and thromb
PMID 23109488

Absence of bi-directional cross-resistance of thrombopoietin receptor agonists in chronic refractory immune thrombocytopenia: possible role of MPL polymorphisms.

Polverelli N, Palandri F, Iacobucci I, Catani L, Martinelli G, Vianelli N.SourceDepartment of Haematology and Clinical Oncology "L. and A. Seràgnoli", S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. nicola.polverelli@gmail.com.
British journal of haematology.Br J Haematol.2012 Dec 29. doi: 10.1111/bjh.12186. [Epub ahead of print]
PMID 23278214

Repeated short-term use of eltrombopag in patients with chronic immune thrombocytopenia (ITP).

Bussel JB, Saleh MN, Vasey SY, Mayer B, Arning M, Stone NL.SourceWeill Medical College of Cornell University, New York, NY, USA.
British journal of haematology.Br J Haematol.2012 Dec 24. doi: 10.1111/bjh.12169. [Epub ahead of print]
Eltrombopag is a thrombopoietin-receptor agonist that stimulates platelet production and increases platelet counts in patients with chronic immune thrombocytopenia (ITP). This open-label, single-arm study evaluated consistency of response and safety following repeated intermittent dosing of eltrombo
PMID 23278590

Japanese Journal

血小板増加薬としてのトロンボポエチン受容体作動薬とその使い方

冨山佳昭
最新医学 67(9), 2056-2062, 2012-09-00
NAID 40019431067

抗トロンボポエチン受容体抗体と無巨核球性血小板減少症 (AYUMI 自己免疫疾患 : 自己抗体の認識抗原と病因的意義)

桑名正隆
医学のあゆみ 242(8), 584-588, 2012-08-25
NAID 40019381300

Industrial Info. 慢性ITPに対するトロンボポエチン受容体作動薬 : ロミプロスチムについて

柳田誠,古屋良宏,桑澤宏 [他]
細胞 44(9), 409-413, 2012-08-00
NAID 40019408416

Related Pictures

★リンクテーブル★

リンク元	「トロンボポエチン受容体」「CD110」
関連記事	「thrombopoietin」

「トロンボポエチン受容体」

MPL proto-oncogene, thrombopoietin receptor
Identifiers
Aliases	MPL, C-CD110, MPLV, THCYT2, TPOR
External IDs	MGI: 97076 HomoloGene: 7845 GeneCards: 4352
Gene ontology
Molecular function	• cytokine receptor activity; • protein binding; • transmembrane signaling receptor activity; • thrombopoietin receptor activity;
Cellular component	• integral component of membrane; • cell surface; • plasma membrane; • Golgi apparatus; • integral component of plasma membrane; • membrane;
Biological process	• platelet activation; • thrombopoietin-mediated signaling pathway; • cell surface receptor signaling pathway; • blood coagulation; • cell proliferation; • cytokine-mediated signaling pathway;
	Sources:Amigo / QuickGO
RNA expression pattern
	; ; ; ;
	More reference expression data
Orthologs
	4352
	17480
	ENSG00000117400
	ENSMUSG00000006389
	P40238
	Q08351
	NM_005373
	NM_001122949; NM_001285496; NM_001285497; NM_010823
	NP_005364.1
	NP_001116421.1; NP_001272425.1; NP_001272426.1; NP_034953.2
	Wikidata
View/Edit Human	View/Edit Mouse