TFPI beta, a second product from the mouse tissue factor pathway inhibitor(TFPI) gene

Tissue factor pathway inhibitor (TFPI) contains three Kunitz domains separa ted by two connecting regions. We have cloned another naturally occurring T FPI gene product from a mouse lung cDNA library which we have called TFPI b eta. TFPI beta is derived from alternative splicing of the TFPI gene. Analy sis of the cDNA shows that mouse TFPI beta protein is identical to TFPI fro m the N'-terminus through the second connecting region. However, mouse TFPI beta possesses neither a third Kunitz domain nor an Arg, Lys-rich C'-termi nus but instead has a completely different C'-terminal (beta-domain) sequen ce which is not homologous to any known protein. Northern blot analyses sho w that the tissues for mouse TFPI beta synthesis are heart and lung; in con trast, TFPI appears in Northern blots of heart and spleen. Both TFPI beta a nd TFPI messages first appear in 7-day-old mouse embryos, but only the TFPI mRNA persists until 17 days. Purified recombinant TFPI beta shows an appar ent molecular weight of 38 kDa. Kinetic studies indicate that mouse TFPI be ta is a slow-binding enzyme inhibitor for human factor Xa. in addition, hep arin does not enhance the inhibition of factor Xa by mouse TFPI beta althou gh it does accelerate factor Xa inhibition by TFPI.