Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S-C4b binding protein complex.

@article{Rezende2004CoagulationIA,
  title={Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S-C4b binding protein complex.},
  author={Suely Meireles Rezende and R. Simmonds and David A. Lane},
  journal={Blood},
  year={2004},
  volume={103 4},
  pages={
          1192-201
        }
}
Protein S (PS) has an established role as an important cofactor to activated protein C (APC) in the degradation of coagulation cofactors Va and VIIIa. This anticoagulant role is evident from the consequences of its deficiency, when there is an increased risk of venous thromboembolism. In human plasma, PS circulates approximately 40% as free PS (FPS) and 60% in complex with C4b-binding protein (C4BP). Formation of this complex results in loss of PS cofactor function, and C4BP can then modulate… 

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References

SHOWING 1-10 OF 192 REFERENCES

Vitamin K-Dependent Protein S Localizing Complement Regulator C4b-Binding Protein to the Surface of Apoptotic Cells1

The C4BP that was bound via protein S to the apoptotic cells was able to interact with the complement protein C4b, supporting a physiological role of the C4 BP/protein S complex in regulation of complement on the surface of apoptotic cell surface.

Protein S and the regulation of activated protein C.

  • F. Walker
  • Biology
    Seminars in thrombosis and hemostasis
  • 1984
It is suggested that protein S can function as a cofactor protein in the activated protein C catalyzed inactivation of Factor Va and appears to be important in the regulation of the plasma anticoagulant activity ofactivated protein C as well.

Protein S enhances C4b binding protein interaction with neutrophils.

Results indicate that the protein S-C4bBP complex binds to the neutrophil surface where it can presumably modulate complement assembly on the cell surface.

Protein S and C4b-binding protein: components involved in the regulation of the protein C anticoagulant system.

Anticoagulation may not be the sole function of protein S, since both in vivo and in vitro, it forms a high affinity non-covalent complex with one of the regulatory proteins in the complement system, the C4b-binding protein (C4BP).

The interaction of protein S with the phospholipid surface is essential for the activated protein C-independent activity of protein S.

High affinity interactions of protein S with the membrane surface are essential for the direct anticoagulant activity ofprotein S and it is suggested that inhibition of the prothrombinase and the tenase complex byprotein S is a consequence of the occupation of the phospholipid surface by protein S molecules.

Visualization of human C4b-binding protein and its complexes with vitamin K-dependent protein S and complement protein C4b.

C4b-binding protein (C4bp) participates in the regulation of the C3 convertase of the classical pathway of complement. By binding to C4b, which is one of the structural subunits of this enzyme, C4bp

Cellular effects and signalling pathways activated by the anti-coagulant factor, protein S, in vascular cells protein S cellular effects.

The synthesis and secretion of protein S by endothelial cells suggests that in addition to its role in the coagulation cascade, protein S may be an important autocrine factor implicated in the pathophysiology of the vascular system.

Modulation of the classical pathway C3 convertase by plasma proteins C4 binding protein and C3b inactivator.

It is concluded that C4 binding protein and C3b inactivator control the C3 convertase of the classical pathway in a fashion similar to that described for beta 1H and C 3b inActivator in the alternative pathway.

Contributions of Gla and EGF-like domains to the function of vitamin K-dependent coagulation factors.

  • J. Stenflo
  • Biology
    Critical reviews in eukaryotic gene expression
  • 1999
The N-terminal noncatalytic Gla and EGF-like domains that provide the coagulation serine proteases with unique properties, such as affinity for certain biological membranes, and also mediate protein-protein interactions, are the subject of this review.

Factor V and protein S as synergistic cofactors to activated protein C in degradation of factor VIIIa.

The results suggest that factor V and protein S work in synergy as phospholipid-bound cofactors to APC.
...