IDENTIFICATION AND CLONING OF A MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR THAT IS A LIGAND FOR THE CYTOKINE RECEPTOR MPL

A novel megakaryocyte growth and development factor (MGDF) has been id entified in aplastic canine plasma, and its cDNAs have been cloned fro m canine, murine, and human sources. Purified canine MGDF isolated by procedures involving Mpl receptor affinity chromatography exists in at least two forms, with apparent molecular masses of 25 kDa and 31 kDa, that share the N-terminal amino acid sequence APPACDPRLLNKMLRDSHVLH. Human, dog, and mouse cDNAs for MGDF are highly conserved and encode o pen reading frames for proteins of 353, 352, and 356 amino acids, resp ectively, including predicted signal peptides. Canine MGDF and recombi nant human MGDF support the development of megakaryocytes from human C D34(+) progenitor cell populations in liquid culture and promote the s urvival of a factor-dependent murine cell line (32D) engineered to exp ress Mpl. These biological activities are blocked by the soluble extra cellular domain of Mpl. These data demonstrate that MGDF is a novel cy tokine that regulates megakaryocyte development and is a ligand for th e MPI receptor.