Thrombopoietin receptor (TPOR, c-Mpl) is a hematopoietic receptor that binds the growth factor, thrombopoietin (TPO), responsible for regulation of platelet production. Expression of TPOR by megakaryocytes is required for megakaryocyte growth and development. TPOR is also expressed by hematopoietic stem cells and is required for stem cell maintenance and expansion. Studies show that mice lacking either TPOR or TPO have severely reduced numbers of platelets and megakaryocytes as well as decreased numbers of other hematopoietic lineages. Binding of TPO to TPOR induces receptor dimerization that leads to phosphorylation and activation of the tyrosine kinase Jak2. Activated Jak2 associates with the cytoplasmic domain of TPOR and phosphorylates TPOR at Tyr626 and Tyr631. These phosphorylated tyrosine residues provide docking sites for downstream signaling molecules including Stat3, Stat5, Shc, and SHIP.
