MPL
小结
MPL编码蛋白是血小板生成素受体，也称为骨髓增生性白血病原癌基因。血小板生成素通过与其配体结合而激活，进而导致JAK / STAT途径的激活。正常受体蛋白在巨核细胞的生长和调节和血小板的产生中起关键作用。在一些实体瘤中报道过MPL存在异常表达。在一个128例结直肠癌患者的研究中，MPL的较高水平表达与肝、肺转移密切相关。然而，在一个118例乳腺肿瘤和29例肺肿瘤的研究中，MPL mRNA是检测不到或者量很少。因此，MPL的具体作用机制还不明确。
MPL gene encodes the MPL proto-oncogene, also known as the thrombopoietin receptor. Activation of the receptor through binding of its ligand, thrombopoietin, results in activation of the JAK/STAT pathway.MPL encodes for the myeloproliferative leukemia proto-oncogene, thrombopoietin receptor. The gene was first identified in as the oncogene v-mpl, from the murine myeloproliferative leukemia virus that transformed hematopoietic cells from the bone marrow in mice. The normal receptor protein is critical in growth and regulation of megakaryocytes and platelet production. The gene is a transmembrane protein with an extracellular cytokine binding domain and intracellular cytokine signaling domains. Binding of its ligand, thrombopoietin (TPO), results in receptor dimerization and activation of the JAK family of tyrosine kinases; this leads to activation of the STAT family of transcription factors. The MAPK pathway can also be activated as a result of receptor activation. The most common mutations, W515L and W515K, which activate receptor signaling are found in myeloproliferative neoplasms such as essential thrombocytosis and myelofibrosis. Aberrant expression of MPL has been reported in some solid tumors. In a study of 128 colorectal cancer cases, higher MPL expression was associated with metastasis to liver and lung. However, in a study of 118 breast tumors and 29 lung tumors, MPL mRNA was either not detectable or at very low levels. The thromobopoietin receptor can be activated by administration of drug agonists such as eltrombopag and romiplostim. These therapies have been approved for the treatment of idiopathic thrombocytopenic purpura (ITP).