The interaction between complement component C4b-binding protein and the vitamin K-dependent protein S forms a link between blood coagulation and the complement system.

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The interaction between complement component C4b-binding protein and the vitamin K-dependent protein S forms a link between blood coagulation and the complement system.

Publication Date
Aug 01, 1991
Source
PMC
Keywords
Disciplines
  • Biology
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Abstract

Biochem. J. (1991) 277, 581-592 (Printed in Great Britain) REVIEW ARTICLE The interaction between complement component C4b-binding protein and the vitamin K-dependent protein S forms a link between blood coagulation and the complement system Martin HESSING* Department of Haematology, University Hospital Utrecht, Utrecht, The Netherlands INTRODUCTION Blood coagulation is a complex of reactions, which involves several enzymes, cofactor proteins, phospholipid surfaces and Ca2+ ions. This waterfall or cascade system is initiated upon exposure of blood to tissue factor or negatively charged surfaces. Then the intrinsic or the extrinsic pathway of coagulation are initiated, leading to the formation of thrombin and fibrin. This clotting cascade prevents excessive bleeding upon injury (Furie & Furie, 1988; Mann et al., 1988). Another example of a cascade system is the complement system, which is composed of two pathways: the classical pathway and the alternative pathway (Lachmann & Hughes-Jones, 1985). The classical pathway is activated by immune complexes and the alternative pathway by activating surfaces such as the surface of a micro-organism. One of the main functions of the complement system is the lysis of target cells (Muller-Eberhard & Miescher, 1985; Law & Reid, 1988). In recent years most of the components of both systems have been purified and the molecular interactions that are required for the catalytic events that occur at each step of the cascades have been characterized. Although both cascade systems are composed of many different proteins, there are only few interactions known between them. In fact, the interaction between complement component C4, C4b-binding protein (C4BP) and protein S constitutes a unique link between the complement and coagulation systems (Fig. 1). This review deals with the structural and functional relationships of C4, C4BP and protein S, and their regulation. In addition, the short consensus repeat (SCR) domains of C4BP will be discussed in context of other SCR-

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