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Thromb Haemost 1998; 80(04): 585-587
DOI: 10.1055/s-0037-1615425
Rapid Communication
Schattauer GmbH

Activity of Secreted Kunitz Domain 1 Variants of Tissue Factor Pathway Inhibitor

Kirk Johnson   *
,
Isabel Zaror   *
,
Diane Bauer
1   From the Chiron Technologies, Chiron Corporation, Emeryville, CA, USA
,
Yoon Choi
1   From the Chiron Technologies, Chiron Corporation, Emeryville, CA, USA
,
Abla Creasey
1   From the Chiron Technologies, Chiron Corporation, Emeryville, CA, USA
,
Michael Innis
1   From the Chiron Technologies, Chiron Corporation, Emeryville, CA, USA
› Author Affiliations
Further Information

Publication History

Received 30 June 1997

Accepted after resubmission 17 June 1998

Publication Date:
08 December 2017 (online)

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Summary

Tissue factor pathway inhibitors (TFPI and TFPI-2) are Kunitz domain-type serine protease inhibitors which inhibit factor VIIa/tissue factor (VIIa/TF) complexes in a factor Xa-dependent manner. The VIIa/TF and Xa inhibitory activity has been localized to the first two Kunitz domains, respectively. Unlike TFPI, TFPI-2 has been reported to exhibit significant Xa-independent VIIa/TF inhibitory activity, perhaps due to an arginine at the P1 residue in the first Kunitz domain of TFPI-2 as opposed to a lysine at the comparable residue in TFPI. Two domain TFPI variants, differing in the first Kunitz domain but containing the second Kunitz domain of TFPI, were constructed and secreted by Saccharomyces cerevisiae in order to test the possibility that a TFPI first Kunitz domain with a P1 lysine to arginine change or a hybrid containing the TFPI-2 first Kunitz domain may represent more potent VIIa/TF inhibitors. When yeast supernatants were analyzed for specific activity in the Xa-dependent inhibition of VIIa/TF, neither variant was as active as the truncated TFPI.

* Authors contributed equally


 

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