Protese-activated receptor PAR4 (ZCHEMR2)

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues

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530324, 530326, 530327, 530329, C07K 706, C07K 708, C07K 14705

Patent

active

061110752

ABSTRACT:
The present invention relates to polynucleotide and polypeptide molecules for PAR4, a novel member of the protease-activated receptor family. The polypeptides, and polynucleotides encoding them, mediate biological responses and/or cellular signaling in response to proteases. Protease cleavage of PAR4 exposes a PAR4 extracellular amino terminal portion that serves as a ligand for the PAR4 receptor. PAR4 may be used as a target in drug screening, and further used to identify proteinaceous or non-proteinaceous PAR4 agonists and antagonists. The present invention also includes antibodies to the PAR4 polypeptides.

REFERENCES:
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Nystedt, et al., "Molecular cloning of a potential proteinase activated receptor," Proc. Natl. Acad. Sci. USA 91:9208-9212, Sep., 1994.
Vu, et al., "Domains specifying thrombin-receptor interaction," Nature 353:674-677, Oct. 17, 1997.
Connolly, et al., "Role of the thrombin receptor in development and evidence for a second receptor," Nature 381:516-519, Jun. 6, 1996.
Coughlin, "Protease-activated receptors start a family," Proc. Natl. Acad, Sci. USA 91:9200-9202, Sep., 1994.
Molino, et al., "Endothelial cell thrombin receptors and PAR-2," J. Biol. Chem. 272:11133-11141, Apr. 25, 1997.
Gerszten, et al., "Specificity of the thrombin receptor for agonist peptide is defined by its extracellular surface," Nature 368:648-651, Apr. 14, 1994.
Ishii, et al., "Inhibition of thrombin receptor signaling by a G-protein coupled receptor kinase," J. Biol. Chem. 269:1125-1130, Jan. 14, 1994.
Probst, et al., "Sequence alignment of the G-protein coupled receptor superfamily," DNA Cell Biol. 11:1-20, 1997.
Ishihara, et al., "Protease-activated receptor 3 is a second thrombin receptor in humans," Nature 386:502-506, Apr. 3, 1997.
U.S. application No. 09/032397,Coughlin and Kahn, filed 00/0000.

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