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

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 (Mr 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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Lok, S., Kaushansky, K., Holly, R. et al. Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature 369, 565–568 (1994). https://doi.org/10.1038/369565a0

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