Alternatively spliced tissue factor: discovery, insights, clinical implications

Following the molecular cloning of human Tissue Factor (TF) in mid-1980's, great strides have been made in the understanding of TF biology, TF's crucial roles in the initiation of blood coagulation and embryonic development, and TF's contribution to the pathobiology of various disease states. The 21(st) century brought about a rather unexpected turn in the "TF journey" - a few years back it was reported that the TF gene produces not one, but two proteins with distinct structural and functional characteristics. The so-called "full-length TF" (flTF) - a much-studied integral membrane glycoprotein long presumed to be, and experimentally handled as "the TF" in hundreds of laboratories around the world - is now known to be one of the two TF forms naturally occurring in humans as well as mice. The other, recently discovered form is termed alternatively spliced TF (asTF) which, unlike flTF, lacks a transmembrane domain and can thus be secreted. In this review, we summarize the literature on asTF by discussing asTF's biologic roles as they are currently understood, tackling a number of questions pertaining to asTF's evident and proposed biologic properties, and briefly covering the emerging field of regulated TF pre-mRNA processing.