v-mpl is a mouse oncogene that is part of the genome of the myeloproliferative leukemia virus (MPLV). The cellular homolog gene c-mpl encodes an hematopoietic cytokine receptor restricted to the megakaryocytic lineage of differentiation. Using the Mpl receptor protein, cDNAs corresponding to the receptor ligand were isolated in humans, pigs, dogs and mice. In vivo and in vitro, the recombinant molecule has both the thrombopoietin (TPO) and megakaryocyte-colony stimulating factor (MK-CSF) activities. This molecule (Mpl ligand/TPO/MK-CSF) is the humoral physiological regulator of platelet production.