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Thromb Haemost 2000; 83(06): 909-914
DOI: 10.1055/s-0037-1613943
Commentary
Schattauer GmbH

Proteolytic Modulation of Thrombopoietin Activity: Comparison of Thrombin, Plasmin, and Urokinase

Alexander P. Reiner
1   From the Department of Medicine, University of Washington, Seattle, WA, USA
,
Kaelen M. Aramaki
1   From the Department of Medicine, University of Washington, Seattle, WA, USA
› Author Affiliations
Further Information

Publication History

Received 09 June 1999

Accepted after resubmission 28 January 2000

Publication Date:
14 December 2017 (online)

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Summary

Several observations suggest that limited proteolysis of full-length 70 kD human thrombopoietin (Tpo) may be important for Tpo biology. Recently, it was reported that thrombin cleaves full-length recombinant human Tpo (rhTpo) sequentially at two sites, Arg195 within the glycan domain followed by Arg117 within the cytokine domain, and that these cleavages modulate Tpo activity in vitro. We demonstrate that urokinase and plasmin also cleave rhTpo in a time-dependent manner. Urokinase cleavage is confined to the glycan domain, and generates a 35 kD N-terminal fragment that contains the intact cytokine domain, and is associated with increased Tpo activity. In contrast, plasmin cleaves Tpo sequentially at two specific sites (Arg205 within the glycan domain followed by Lys52 within the cytokine domain), and is associated with a marked decrease in Tpo activity. These proteolytic events have potential implications for regulation of Tpo activity in vivo.

Key words

Thrombopoietin - urokinase - plasmin - thrombin - Mpl
 

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