Thrombopoietin (TPO or THPO), also known as c-Mpl ligand (c-Mpl L), is a cytokine that plays a central role in megakaryopoiesis by influencing the development and maturation of megakaryocytes and platelet production. TPO is expressed by both mature and progenitor megakaryocytes, as well as by human platelets. Human TPO cDNA encodes a 332 amino acid precursor with a 21 amino acid signal peptide which is cleaved to generate the mature protein. TPO isolated from serum ranges in molecular weight, which suggests that the protein is highly glycosylated. TPO exerts its biological effects through the TPO receptor, c-Mpl. Stimulation of c-Mpl with TPO results in the activation of the Janus tyrosine kinase family members, Tyk 2 and JAK2 which in turn phosphorylate Stat5 and Stat3, causing their nuclear translocation and the transcription of Stat responsive genes.
