Human phospholipase inhibitor protein

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

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C07K 100

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058115200

ABSTRACT:
The present invention provides a polynucleotide (gipl) the partial sequence for which was initially isolated from a THP-1 cDNA library and which identifies and encodes a novel human phospholipase inhibitor (GIPL). The invention provides for genetically engineered expression vectors and host cells comprising the nucleic acid sequence encoding GIPL. The invention also provides for the use of purified GIPL and its agonists in pharmaceutical compositions for the treatment of diseases associated with the abnormal or excess phospholipase activity. Additionally, the invention provides for the use of antisense molecules to gipl or inhibitors of GIPL in pharmaceutical compositions for the prevention of pregnancy or treatment of Alzheimer's disease. The invention also describes diagnostic assays which utilize diagnostic compositions comprising the polynucleotide, fragments or the complement thereof, which hybridize with the genomic sequence or the transcript of gipl, or anti-GIPL antibodies which specifically bind to the polypeptide, GIPL.

REFERENCES:
patent: 5478857 (1995-12-01), Clemens et al.
de Carvalho et al., "Regulation of Lysophospholipase Activity of the 85kDa Phospholipase A.sub.2 and Activation in Mouse Peritoneal Macrophages", J. Biol. Chem, (1995) 270:20439-20446.
Fortes-Dias et al., "A Phospholipase A.sub.2 Inhibitor from the Plasma of the South American Rattlesnake (Crotalus durissus terrificus)", J. Biol. Chem., (1994) 269:15646-15651.
Gewert et al., "Dexamethansone down-regulates the 85 kDa phospholiphase A.sub.2 in mouse macrophages and suppresses its activation", Biochem. J., (1995), 307;499-504.
Jaattela et al., "Bcl-x and Bcl-2 inhibit TNF and Fas-induced apoptosis and activation of phospholiphase A.sub.2 in breast carcinoma cells", Oncogene, (1995) 10:2297-2305.
Ross et al., "Characterization of a Novel Phospholipase A.sub.2 Activity in Human Brain" J. Neurochem, (1995) 64:2213-2221.
Schalkwijk et al., "Epidermal growth factor (EGF) induces serine phosphorylation-dependent activation and calcium-dependent translocation of the cytosolic phospholipase A.sub.2 " Eur. J. Biochem. (1995) 231:593-601.
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Van den Berg et al., "Solution structure of porcine pancreatic phospholipase A.sub.2 " EMBO J., (1995) 14:4123-4131.
Wijkander et al., "5-Lipoxygenase Procducts Modulate the Activity of the 85-kDa Phospholipase A.sub.2 in Human Neutrophils" J. Biol. Chem., (1995) 270:26543-26549.
Yamada et al., "Phospholipase A.sub.2 -Activating Peptide-Induced Contraction of Smooth Muscle is Mediated by Protein Kinase C-Map Kinase Cascade" Biochem. Biophys. Res. Commun., (1995) 217:203-210.
Ohkura et al., "The two subunits of a phospholipase A.sub.2 inhibitor from the plasma of thailand cobra having structural similarity to urokinase-type plasminogen activator receptor and ly-6 related proteins", Biochem. Biophys. Res. Commun. 204:1212-1218 (1994).
Database EST, Accession No. W39152, Hillier et al., (1996).
Database EST, Accession No. R16683, Hillier et al., Unpublished (1995).

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