NATIVE THROMBOPOIETIN - STRUCTURE AND FUNCTION

Thrombopoietin (TPO), the c-Mpl ligand, is produced constitutively in liver and other organs, circulates in the bloodstream, and is delivere d to bone marrow, where it stimulates the early development of multipl e hematopoietic lineages and megakaryocytopoiesis. The concentration o f TPO in blood is regulated by c-Mpl mass on platelets and megakaryocy tes. In addition to regulation by the number of TPO molecules, includi ng the possible modulation of TPO mRNA abundance in bone marrow, megak aryocytopoiesis and platelet production may be regulated as a result o f modulation of TPO activity by proteolytic processing that generates truncated forms of the molecule. Characterization of TPO partially pur ified from human plasma, however, revealed that the full-length molecu le was the predominant form in the blood of both normal individuals an d thrombocytopenic patients, although small amounts of truncated speci es were detected, Thus, truncation of TPO, at least that in the circul ation examined, does not appear to contribute to the direct regulation of platelet production in response to increased demand. Given that na tive TPO isolated from the plasma of thrombocytopenic animals comprise s truncated forms, the truncation of TPO is likely of physiological im portance in the life history of this molecule.