MPL

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. 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. [provided by RefSeq, Jul 2008]

MPL Proto-Oncogene, Thrombopoietin Receptor

Receptor for thrombopoietin that acts as a primary regulator of megakaryopoiesis and platelet production. May represent a regulatory molecule specific for TPO-R-dependent immune responses.

Basophil homeostasis Source: Ensembl
Cellular response to hypoxia Source: Ensembl
Cytokine-mediated signaling pathway Source: GO_Central
Eosinophil homeostasis Source: Ensembl
Hemopoiesis Source: GO_Central
Monocyte homeostasis Source: Ensembl
Neutrophil homeostasis Source: Ensembl
Platelet aggregation Source: Ensembl
Positive regulation of cell population proliferation Source: GO_Central
Positive regulation of lymphocyte proliferation Source: Ensembl
Positive regulation of platelet formation Source: Ensembl
Thrombopoietin-mediated signaling pathway Source: GO_Central

Plasma membrane
Cell membrane
Golgi apparatus
Other locations
Cell surface

Congenital amegakaryocytic thrombocytopenia (CAMT):
Disease characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies.
Thrombocythemia 2 (THCYT2):
A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes.
Myelofibrosis with myeloid metaplasia (MMM):
A chronic myeloproliferative disorder characterized by replacement of the bone marrow by fibrous tissue, extramedullary hematopoiesis, anemia, leukoerythroblastosis and hepatosplenomegaly.

Extracellular: 26-491
Helical: 492-513
Cytoplasmic: 514-635

Ubiquitination at Lys-553 and Lys-573 targets MPL for degradation by both the lysosomal and proteasomal pathways. The E3 ubiquitin-protein ligase CBL significantly contributes to this ubiquitination.