American Cyanamid Company

Basf Aktiengesellschaft

Wyeth

The United States of America As Represented by the Department of Health

Mark Henry Pausch

John Richard Hadcock

Bradley Alton Ozenberger

Donald R Kirsch

Deborah Tardy Chaleff

Eileen Marie Kajkowski

Laura Price

Laura A Price

Jurgen Wess

Ralph M Cleale, Iv

Expression vectors and yeast cells that contain a heterologous G protein-coupled receptor gene and a gene mutation that causes increased sensitivity to receptor activation or a gene mutation that permits transcriptional activation of pheromone-responsive genes without cell cycle arrest. Methods of making the yeast cells.

Heterologous G protein coupled receptors expressed in yeast, their fusion with G proteins and use thereof in bioassay

The present invention particularly relates to a newly identified murine genomic polynucleotide that encodes an ortholog of the human P2T receptor which is expressed at high levels in the central nervous system, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. The invention relates also to identifying compounds which may be agonists, antagonists and/or inhibitors of P2T, and therefore potentially useful in therapy.

Murine genomic polynucleotide sequence encoding a G-protein coupled receptor and methods of use therefor

This invention relates to mutant G protein-coupled receptors with improved G-protein coupling and receptor response, yeast cells expressing such receptors, vectors useful for making such cells, and methods of making and using same.

Method for improving the function of heterologous G protein-coupled receptors

A first aspect of the present invention is directed to a transformed yeast cell containing a first heterologous DNA sequence which codes for a G protein-coupled receptor, for example, the somatostatin receptor, and a second heterologous DNA sequence which codes for a G protein a subunit or portions thereof fused to DNA sequences from the yeast G protein in a subunit. A second aspect of the present invention is a transformed yeast cell containing a heterologous DNA sequence which codes for a G protein coupled receptor. A third aspect of the present invention is a method of assaying compounds to determine effects on cell growth.

The present invention is directed to expression vectors and yeast cells transformed therewith containing a first heterologous nucleotide sequence which codes for a G protein-coupled receptor, for example, the somatostatin receptor, and a second nucleotide sequence which codes for all or a portion of a G protein &agr;&bgr;&ggr; complex. Said heterologous protein is physically expressed in a host cell membrane in proper orientation for both stereoselective binding of ligands, as well as functional interaction with G proteins on a cytoplasmic side of the cell membrane. In some embodiments, a nucleotide sequence encoding a heterologous or chimeric G&agr; protein is expressed in conjunction with nucleotide sequences from the yeast G protein &bgr;&ggr; subunits. A second aspect of the present invention provides expression vectors and yeast cells transformed therewith encoding chimeric yeast/heterologous G protein coupled receptors. A third aspect of the present invention is directed to methods of assaying compounds using such expression constructs and yeast cell expression systems to determine the effects of ligand binding to the heterologous receptors expressed in the systems.

Method for detecting ligand binding to G protein coupled receptors

There is provided a method for increasing lean meat, improving the lean meat to fat ratio and improving amino acid utilization in warm-blooded animals by administering an effective amount of an alpha-2 adrenergic receptor antagonist.

Method for increasing lean meat, improving the lean meat to fat ratio

The present invention relates to a method for isolating and cloning receptor DNA sequences. The invention also provides novel DNA sequences encoding a novel somatostatin receptor subtype.

Receptor identification method

Somatostatin receptor protein

The present invention is directed to a expression vectors and yeast cells transformed therewith containing a first heterologous nucleotide sequence which codes for a G protein-coupled receptor, for example, the somatostatin receptor, and a second nucleotide sequence which codes for all or a portion of a G protein .alpha..beta..gamma. complex. Said heterologous protein is physically expressed in a host cell membrane in proper orientation for both stereoselective binding of ligands, as well as functional interaction with G proteins on the cytoplasmic side of the cell membrane. In some embodiments, a nucleotide sequence encoding a heterologous or chimeric G.alpha. protein is expressed in conjunction with nucleotide sequences from the yeast G protein .beta..gamma. subunits. A second aspect of the present invention provides expression vectors and transformed yeast cells encoding chimeric yeast/heterologous G protein coupled receptors. A third aspect of the present invention is directed to methods of assaying compounds using these expression constructs and yeast cell expression systems to determine the effects of ligand binding to the heterologous receptors expressed in the systems.

Recombinant expression vectors for expression of heterologous proteins

A first aspect of the present invention is directed to a transformed yeast cell containing a first heterologous DNA sequence which codes for a G protein-coupled receptor, for example, the somatostatin receptor, and a second heterologous DNA sequence which codes for a G protein .alpha. subunit or portions thereof fused to DNA sequences from the yeast G protein a subunit. A second aspect of the present invention is a transformed yeast cell containing a heterologous DNA sequence which codes for a G protein coupled receptor. A third aspect of the present invention is a method of assaying compounds to determine effects on cell growth.

Transformed yeast cells expressing heterologous G-protein coupled

Somatostatin receptors

A first aspect of the present invention is the isolation and characterization of invertebrate (i.e. insect and nematode) potassium channel genes. The present invention provides for the isolation of complementary DNA fragments from Drosophila melanogaster and Caenorhabditis elegans which encode conserved amino acid sequence elements unique to the potassium channel gene family. A yeast expression technology is employed to clone cDNAs from Drosophila melanogaster and a hybridization approach is utilized to isolate additional cDNAs from Caenorhabditis elegans. Using the yeast expression technology, a single 2463 base pair cDNA fragment designated Dm ORF1 is isolated.

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Robbinsville, NJ, United States of America

Mark Henry Pausch