Cloning and regulation of an endothelial cell protein C/activate

Details Cloning and regulation of an endothelial cell protein C/activate Cloning and regulation of an endothelial cell protein C/activate

1997-06-18

1998-12-22

Hutzell, Paula K.

Chemistry: natural resins or derivatives; peptides or proteins;

Proteins, i.e., more than 100 amino acid residues

530380, C07K 14705

Patent

active

058521712

ABSTRACT:
Human protein C and activated protein C were shown to bind to endothelium specifically, selectively and saturably (Kd=30 nM, 7000 sites per cell) in a Ca.sup.2+ dependent fashion. Expression cloning revealed a 1.3 kb CDNA that coded for a novel type I transmembrane glycoprotein capable of binding protein C. This protein appears to be a member of the CD1/MHC superfamily. Like thrombomodulin, the receptor involved in protein C activation, the endothelial cell protein C receptor (EPCR) function and message are both down regulated by exposure of endothelium to TNF. Identification of EPCR as a member of the CD1/MHC superfamily provides insights into the role of protein C in regulating the inflammatory response, and determination of methods for pharmaceutical use in manipulating the inflammatory response.

REFERENCES:
Ecke et al. Agents & Actions, Supp., vol. 38, pp. 182-189 (Abstract Only), 1992.

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