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Functional Evolution of Tissue Factor, the Archetype of the Cytokine Receptor Family

[ Vol. 6 , Issue. 6 ]


C. A. Spek, M. V. Zoelen, S. H. Diks and M. P. Peppelenbosch   Pages 367 - 373 ( 7 )


Already in the 19th century, it was accepted that tissues display clot-promoting activity. The awareness that a single protein was accountable for this pro-coagulant effect led to the detection of tissue factor (tissue factor), but for many years it was thought that tissue factor activity was restricted to the activation of an auxiliary pathway that had little biological significance. Today tissue factor is recognised to be the primary biological initiator of the coagulation cascade. In silico studies have highlighted the high degree of structural similarity of tissue factor with the super family of interferon receptors. The cytokine class II receptor family has probably evolved from an ancient gene coding for a pre-eukaryotic extracellular protein. Tissue factor evolved from this protein and matching sequences are found in invertebrates, especially insects. From tissue factor, the other receptors evolved. Strikingly, the common evolutionary origin of tissue factor and cytokine receptors is reflected in identical signalling. The evolutionary origin of tissue factor is the subject of the present review.


Chordates, cytokines receptors, tissue factor, prokariotic secretion system 2


Laboratory for Experimental Internal Medicine, Academic Medical Center,Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;

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