• Source: Thrombopoietin receptor

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.




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.




Interactions


Myeloproliferative leukemia virus oncogene has been shown to interact with:

ATXN2L
JAK2
thrombopoietin




Clinical relevance


Inactivating mutations in this gene have been shown to cause familial aplastic anemia.
Specific mutations to this gene are associated with myelofibrosis and essential thrombocythemia. In essential thrombocythemia, mutations occur at position 505 or 515 in the protein. In myelofibrosis, a mutation occurs at position 515.
These mutations lead to the production of thrombopoietin receptors that are permanently activated, which results in the overproduction of abnormal megakaryocytes.




See also


Cluster of differentiation
Congenital amegakaryocytic thrombocytopenia




References






Further reading






External links


MPL+protein,+human at the U.S. 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.

Kata Kunci Pencarian:

• Thrombopoietin receptor
• Thrombopoietin
• Immune thrombocytopenic purpura
• Eltrombopag
• Avatrombopag
• Thrombopoietin mimetics
• Primary myelofibrosis
• Ectodysplasin A receptor
• Myeloproliferative neoplasm
• Hetrombopag