Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1997-11-18
1999-01-05
Wax, Robert A.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
435194, 4352523, 435 691, 530350, 530859, 536 235, C12P 2106, C12N 912, C12N 120, C07H 2104
Patent
active
058561331
ABSTRACT:
The present invention relates to the discovery, identification and characterization of nucleotides that encode the G protein regulated phosphatidylinositol-3'kinase, a heterodimeric enzyme which produces the intracellular messenger phosphatidylinositol (3,4,5)-triphosphate in response to activation of trimeric G protein-linked receptors. This novel protein, comprised of a catalytic subunit, p120, and a regulatory subunit, p101, is found in cells of hematopoietic origin and is involved in immune system responses which cause inflammation. The presence of p101 subunit is largely responsible for the dramatic stimulation of kinase activity in the presence of activated trimeric G proteins. The invention encompasses p101 and p120 nucleotides, host cell expression systems, p101 and p120 proteins, fusion proteins, polypeptides and peptides, antibodies to these proteins, transgenic animals that express a p101 or 120 transgene, or recombinant knockout cells and animals that do not express the p101 or p120 gene, antagonists and agonists of the enzyme, and other compounds that modulate p101 or p120 gene expression or enzyme activity that can be used for diagnosis, drug screening, clinical trial monitoring, and/or the treatment of inflammatory disorders.
REFERENCES:
Acaro et al., 1993, "Wortmannin is a Potent Phosphatidylisositol 3-Kinase Inhibitor: the Role of Phosphatidylinositol 3,4,5-trisphosphate in Neutrophil Responses," Biochem J. 296:297-301.
Chen et al., 1995, "A Region of Adenylyl Cyclase 2 Critical for Regular by G Protein .beta..gamma. Subunits", Science 268:1166-1169.
Gura, 1996, "Chemokines Take Center Stage in Inflammatory Ills," Science 272:954-956.
Inukai et al., 1995, "A Novel 55-kDA Regulatory Subunit for Phosphatidlyinositol 3-Kinase Structurally Similiar to p55PIK Is Generated by Alternative Splicing of the p85.alpha. Gene", J. Biol. Chem. 271:5317-5320.
Kurosu et al., 1995, "Radiolabeling of Catalytic Subunits of PI 3-Kinases of the G.beta..gamma.-Sensitive Isoform as a Complex Composed of 46-kDa and 100-kDa Subunits," Biochem. Biophys. Res. Commun. 216:655-661.
Morris et al., 1995, "Regulation of Phosphoinositide-3 Kinase by G Protein .beta..gamma.-Subunits in a Rat Osteosarcoma Cell Line," Molecular Pharmacology 48:532-539.
Otsu et al., 1991,"Characterization of Two 85 kd Proteins That Associate with Receptor Tyrosine Kinases, Middle-T/pp50.sup.c-src Complexes, and PI3-Kinase", Cell 65:91-1-4.
Pons et al., 1995, "The Structure and Function of p55.sup.PIK Reveal a New Regulatory Subunit for Phosphatidylinositol 3-Kinase", Mol. Cell. Biol. 15:4453-4465.
Rodriguez-Viciana et al., 1994, "Phosphatidylinositol-3-Oh Kinase as a Direct Target of Ras," Science 370:527-532.
Schu et al., 1993, "Phosphatidylinositol 3-Kinase Encoded by Yeast VPS34 Gene Essential for Protein Sorting," Science 260:88-91.
Shaw et al., 1996, "The Plekstrin Homology Domain: An Intrguing Multifunctional Protein Module", Bioassays 18:35-46.
Songyang et al., 1993, "SH2 Domains Recognize Specific Phosphopeptide Sequences", Cell 72:767-778.
Staub et al., 1996, "WW Domains", Structure 4:495-499.
Stephens et al., Feb. 29, 1996, "A Heterotrimeric GTPase-Regulated Isoform of PI3K and the Regulation of its Potential Effectors" Phil. Trans. R Soc. Lond. B 351:211-215.
Stephens et al., Apr. 4, 1997, "The GBY Sensitivity of a PI3K is Dependent Upon a Tightly Associated Adaptor, p. 101," Cell 89:105-114.
Stephens et al., 1994, "A Novel Phosphoinositide 3 Kinase Activity in Myeloid-Derived Cells is Acitivated by G Protein .beta..gamma. Subunits," Cell 77:83-93.
Stephens et al., 1991, "Pathway of Phosphatidylinosito(3,4,5)-Trisphosphate Synthesis in Activated Neutrophis," Nature 351:33-38.
Stephens et al., "Agonist-Stimulated Synthesis of Phosphatidylinositol(3,4,5)-Trisphosphate: A New Intracellular Signing System?," Biochem. Biophys. Acta 1179:27-75.
Stoyanov et al., 1995, "Cloning and Characterization of a G Protein-Activated Human Phosphoinositide-3 Kinase," Cell 269:690-693.
Thelan et al., 1994, "Wortmannin Binds Specifically to 1-Phosphatidylinositol 3-Kinase while Inhibiting Suanine Nucleotide-Binding Protein-Coupled Receptor Signaling in Neutrophil Leukoxytes," Proc. Natl. Acad. Sci. USA 91:4960-4964.
Thomason et al., 1994, "A G-Protein .beta..gamma. -Subunit-Responsive Phosphoinositide 3-Kinase Activity in Human Platelet Cytosol," J. Biol. Chem. 269:16525-16528.
Touhara et al., 1994, "Binding of G Protein .beta..gamma.-Subunits to Pleckstrin Homology", J. Biol. Chem. 269:10217.
Volinia et al., 1995, "A Human Phosphatidylinositol 3-Kinase Complex Related to the Yeast Vps34p-Vps15p Protein Sorting System, " EMBO J. 14:3339-3348.
Yano et al., 1993, "Inhibition of Histamine Secretion by Wortmannnin through the Blockade of Phosphatidylinositol 3-Kinase in RBL-2H3 Cells," J. Biol. Chem. 368:25846-25856.
Hawkins Phillip Thomas
Stephens Len
Onyx Pharmaceuticals
Slobodyansky Elizabeth
Wax Robert A.
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