Decryption of tissue factor.

Tissue factor (TF) is a transmembrane protein which, in complex with factor (F)VIIa, initiates blood coagulation. Numerous studies have determined TF epitopes and individual amino acids which play an important role in the TF/FVIIa complex formation and its activity towards natural substrates. However the subject of cell-surface TF activity remains controversial. It has been almost commonly accepted that TF on the cell surface has low (if any) activity, i.e. is encrypted and requires specific conditions/reagents to become active, i.e. decrypted. One of the leading theories suggests that cell membrane lipid composition plays a crucial role in TF decryption, whereas another assigns the key role to the formation of the Cys(186)-Cys(209) disulfide bond. Despite a number of studies published from several laboratories, the role of this bond in the activity of the TF/FVIIa complex remains elusive and controversial. One of the causes of this controversy could be related to the lack of specificity of the reagents used for the cell treatment leading to possible alterations in other cell surface proteins and cell membrane environment. In conclusion, the influence of the Cys(186)-Cys(209) this bond on cell surface TF function remains unclear.