Thrombopoietin R/TPO R His Tag Protein, Human

The thrombopoietin receptor (TPO-R), also known as MPL, is a member of the type I cytokine receptor superfamily expressed as a homodimer on hematopoietic stem cells and megakaryocytes. Its extracellular domain comprises two cytokine receptor modules and a WSXWS motif, while the intracellular region contains Box1/Box2 motifs that recruit JAK2. Upon TPO ligand binding, the receptor undergoes conformational rearrangement that activates the JAK2-STAT5, PI3K-AKT, and MAPK-ERK signaling cascades, thereby governing hematopoietic stem cell self-renewal, megakaryocyte commitment, and platelet production. Clinically, activating MPL mutations (e.g., W515L) or mutant calreticulin-driven aberrant TPO-R signaling promote myeloproliferative neoplasms, whereas loss-of-function MPL mutations cause congenital amegakaryocytic thrombocytopenia (CAMT). Targeted TPO-R agonists—including the non-peptide small molecule eltrombopag and the peptide agent romiplostim—are approved for immune thrombocytopenia and aplastic anemia, establishing MPL as a pivotal molecular bridge linking fundamental receptor biology to clinical hematologic therapeutics.