Human Thrombopoietin R/Tpo R Alexa Fluor™ Plus 488‑conjugated Antibody

Thrombopoietin receptor (Tpo R), also known as myeloproliferative leukemia protein (c-mpl), is a 95 kDa type I transmembrane protein that is a member of the type I cytokine receptor family within the hematopoietin/cytokine receptor superfamily (1‑4). The 635 amino acid (aa) full-length human Tpo R contains a 25 aa signal sequence, a 466 aa extracellular domain with a ligand binding domain and two fibronectin type III domains, a transmembrane (TM) domain and a cytoplasmic domain. The extracellular domain of human Tpo R shares 78%, 76%, 81%, 82% and 80% aa identity with mouse, rat, bovine, canine and equine Tpo R, respectively. Humans produce three distinct mRNA species; a P-form, a K-form, and a truncated form (Mpl-tr) lacking a TM domain (3‑7). The P-form encodes the full-length receptor. The Mpl-tr form, which is expressed in both human and mouse, is intracellular and targets the P-form for degradation (5, 6). The 579 aa K-form has an alternate cytoplasmic domain, but does not dimerize with, or inhibit, the P-form (7). Thrombopoietin (Tpo) is a key regulator of megakaryocytopoiesis, thrombopoiesis and hematopoietic stem cell self-renewal, as reflected by expression of the Tpo R on megakaryocytes, platelets and hematopoietic progenitors (2, 8). Receptor dimerization occurs upon Tpo binding and initiates signaling through the Ras/MAP and JAK/STAT pathways (1, 2). Internalization and degradation of Tpo following Tpo R binding serves to downregulate circulating Tpo (9). Tpo R expressed at low levels on endothelial cells does not appear to contribute to regulation of Tpo (10). Inactivating mutations of Tpo R cause thrombocytopenia, and absence of functional Tpo R is lethal in humans, but not mice. Other mutations, including an activating change in the TM domain, can cause thrombocytosis (11, 12).