Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo

ZymoGenetics Corporation, Seattle, Washington 98105.
06/1994; 369(6481):565-568. DOI: 10.1038/369565a0

ABSTRACT THE major regulator of circulating platelet levels is believed to be a cytokine termed thrombopoietin1,2. It is thought to be a lineage-specific cytokine affecting the proliferation and maturation of committed cells resulting in the production of megakaryocytes and platelets. Despite considerable efforts by a number of laboratories, the unequivocal identification of thrombopoietin has proven elusive. Here we report the functional cloning of a murine complementary DNA encoding a ligand for the receptor encoded by the c-mpl proto-oncogene (c-Mpl) 3–5. The encoded polypeptide has a predicted molecular mass of 35,000 (M
r 35K). The protein has a novel two-domain structure with an amino-terminal domain homologous with erythropoietin and a carboxy-terminal domain rich in serine, threonine and proline residues and containing seven potential N-linked glycosylation sites. Intraperitoneal injections of mice with recombinant protein increase circulating platelet levels by greater than fourfold after 7 days. These results along with those presented in the accompanying report strongly suggest that the ligand for c-Mpl is thrombopoietin.

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