Posttranslational modifications of tissue factor.
Tissue factor (TF), a membrane protein, is an initiator of blood coagulation in vivo. In this review we discuss how posttranslational modifications affect activity and other properties of TF. Glycosylation of the extracellular domain and the composition of carbohydrates at three glycosylation sites have an influence on TF activity in the extrinsic FXase by increasing the rate of FX proteolysis. No influence of TF glycosylation on the activity of the FVIIa/TF complex towards small synthetic substrates was observed, suggesting that glycosylation has no effect on TF interaction with FVIIa. There are no published data suggesting a direct influence of phosphorylation or palmitoylation in the cytoplasmic domain on TF procoagulant activity. There has been a debate in the recent literature related to the role and formation of the Cys¹⁸⁶-Cys²⁰⁹ disulfide bond. Published opinions from various laboratories range from this bond being essential for the expression of cell TF activity to having no role in it. Overall, it is clear that some modifications of TF have an effect on TF procoagulant activity, signaling functions and trafficking. The influences of other modifications are debatable.
Department of Biochemistry, College of Medicine, University of Vermont, Burlington, VT 05446, USA. sbutenas@uvm.edu
Saulius
S
Butenas
Jolanta
J
Amblo-Krudysz
Kenneth G
KG
Mann
D000818:Animals; D004220:Disulfides / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D019308:Palmitic Acid / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D013925:Thromboplastin / Q000378:metabolism*
D004220:Disulfides; D019308:Palmitic Acid; D013925:Thromboplastin