Summary
Tissue factor pathway inhibitor (TFPI) contains three Kunitz domains separated by
two connecting regions. We have cloned another naturally occurring TFPI gene product
from a mouse lung cDNA library which we have called TFPI β. TFPIβ is derived from
alternative splicing of the TFPI gene. Analysis of the cDNA shows that mouse TFPIβ
protein is identical to TFPI from the N’-terminus through the second connecting region.
However, mouse TFPIβ possesses neither a third Kunitz domain nor an Arg, Lys-rich
C’-terminus but instead has a completely different C’-terminal (β-domain) sequence
which is not homologous to any known protein. Northern blot analyses show that the
tissues for mouse TFPIβ synthesis are heart and lung; in contrast, TFPI appears in
Northern blots of heart and spleen. Both TFPIβ and TFPI messages first appear in 7-day-old
mouse embryos, but only the TFPI mRNA persists until 17 days. Purified recombinant
TFPIβ shows an apparent molecular weight of 38 kDa. Kinetic studies indicate that
mouse TFPIβ is a slow-binding enzyme inhibitor for human factor Xa. In addition, heparin
does not enhance the inhibition of factor Xa by mouse TFPIβ although it does accelerate
factor Xa inhibition by TFPI.