TFPIβ, a Second Product from the Mouse Tissue Factor Pathway Inhibitor (TFPI) Gene

Abstract

SummaryTissue 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.