Myeloproliferative Leukemia Virus Oncogene (MPL)

CD110; C-MPL; MPLV; TPOR; Thrombopoietin Receptor; Myeloproliferative leukemia protein; Proto-oncogene c-Mpl

SPN	V366
HGNC	7217
MGI	97076
PubMed	24043765
RGD	1311069
UniProt	P40238
Wiki	MPL

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.

Reference

"Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene: identification of a member of the hematopoietic growth factor receptor superfamily."
Proc. Natl. Acad. Sci. U.S.A. 89:5640-5644(1992) [PubMed] [Europe PMC] [Abstract]

"Structure and transcription of the human c-mpl gene (MPL)."
Genomics 20:5-12(1994) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and biological annotation of human chromosome 1."
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]

"Ubiquitination and degradation of the thrombopoietin receptor c-Mpl."
Blood 115:1254-1263(2010) [PubMed] [Europe PMC] [Abstract]

"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]

Erratum
Nat. Genet. 23:373-373(1999)

"Cloning and characterization of a family of proteins associated with Mpl."
J. Biol. Chem. 277:9139-9147(2002) [PubMed] [Europe PMC] [Abstract]

"Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin."
Blood 103:4198-4200(2004) [PubMed] [Europe PMC] [Abstract]

"Mpl Baltimore: a thrombopoietin receptor polymorphism associated with thrombocytosis."
Proc. Natl. Acad. Sci. U.S.A. 101:11444-11447(2004) [PubMed] [Europe PMC] [Abstract]

"MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients."
Blood 108:3472-3476(2006) [PubMed] [Europe PMC] [Abstract]

"MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease."
Hum. Mutat. 27:296-296(2006) [PubMed] [Europe PMC] [Abstract]

"MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia."
PLoS Med. 3:E270-E270(2006) [PubMed] [Europe PMC] [Abstract]

"The Asn505 mutation of the c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity."
Blood 114:3325-3328(2009) [PubMed] [Europe PMC] [Abstract]

"MPL W515L mutation in pediatric essential thrombocythemia."
Pediatr. Blood Cancer 60:E52-E54(2013) [PubMed] [Europe PMC] [Abstract]

"The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis."
Blood 125:1159-1169(2015) [PubMed] [Europe PMC] [Abstract]