Abstract: Yeast cells are engineered to express both a surrogate of a pheromone system protein (e.g., enzymes involved in maturation of ?-factor, transporters of a-factor, pheromone receptors, etc.) and a potential peptide modulator of the surrogate, in such a manner that the inhibition or activation of the surrogate affects a screenable or selectable trait of the yeast cells. Various additional features improve the signal-to-noise ratio of the screening/selection system.

Abstract: The present invention pertains to novel yeast cells which are useful for the expression of heterologous G protein coupled receptors. The yeast cells of the present invention can be used in screening assays which can be used to screen for modulators of G protein coupled receptors. Specifically, the invention provides novel yeast cells which express a heterologous G protein coupled receptor and mutant and/or chimeric G protein subunit molecules which serve to functionally integrate the heterologous into the pheromone signaling pathway of the yeast cell. The invention also provides for the expression of heterologous G protein coupled receptors which are functionally integrated into the yeast cell membrane using a yeast ? factor leader sequence. Drug discovery assays using the subject yeast cells are also provided.

Abstract: Yeast cells are engineered to express both a surrogate of a pheromone system protein (e.g., enzymes involved in maturation of ?-factor, transporters of a-factor, pheromone receptors, etc.) and a potential peptide modulator of the surrogate, in such a manner that the inhibition or activation of the surrogate affects a screenable or selectable trait of the yeast cells. Various additional features improve the signal-to-noise ratio of the screening/selection system.

Abstract: The present invention pertains to novel yeast cells which are useful for the expression of heterologous G protein coupled receptors. The yeast cells of the present invention can be used in screening assays which can be used to screen for modulators of G protein coupled receptors. Specifically, the invention provides novel yeast cells which express a heterologous G protein coupled receptor and mutant and/or chimeric G protein subunit molecules which serve to functionally integrate the heterologous into the pheromone signaling pathway of the yeast cell. The invention also provides for the expression of heterologous G protein coupled receptors which are functionally integrated into the yeast cell membrane using a yeast ? factor leader sequence. Drug discovery assays using the subject yeast cells are also provided.

Abstract: The present invention makes available rapid, effective assays for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular receptor or ion channel. The subject assays enable rapid screening of large numbers of polypeptides in a library to identify those polypeptides which induce or antagonize receptor bioactivity. The subject assays are particularly amenable for identifying agonists and antagonists for orphan receptors. In particular the present invention makes available novel ligand agonists of human formyl peptide receptor like-1 (FPRL-1) receptors. These novel ligand agonists are used in the assays of the invention to identify modulators of FPRL-1 receptor.

Abstract: The invention provides recombinant cells that have been engineered such that ligand stimulation of a receptor expressed by the cells leads to amplified signal transduction responses. In one embodiment, the receptor-expressing cells have been engineered to carry a heterologous DNA construct comprising a gene encoding a protein that activates the signal transduction pathway, which gene is operatively linked to a promoter that is responsive to activation of the signal transduction pathway. Stimulation of the receptor by a ligand leads to expression of the heterologous DNA construct encoding the protein that activates the signal transduction pathway such that signals generated by ligand binding to the receptor are amplified. Preferred cells are yeast cells expressing heterologous G protein coupled receptors functionally coupled to the yeast pheromone response pathway and overexpressing Ste5p, Ste4p, Ste12p, Ste11p or a dominant truncation allele of Ste20 via a pheromone-responsive promoter.

Abstract: The present invention makes available a rapid, effective assay for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular receptor or ion channel. The subject assay enables rapid screening of large numbers of polypeptides in a library to identifying those polypeptides which induce or antagonize receptor bioactivity. The subject assay is particularly amenable for identifying surrogate ligands for orphan receptors.

Abstract: Yeast cells are engineered to express both a surrogate of a pheromone system protein (e.g., enzymes involved in maturation of ?-factor, transporters of a-factor, pheromone receptors, etc.) and a potential peptide modulator of the surrogate, in such a manner that the inhibition or activation of the surrogate affects a screenable or selectable trait of the yeast cells. Various additional features improve the signal-to-noise ratio of the screening/selection system.

Abstract: The present invention makes available a rapid, reproducible, robust assay system for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular protein, e.g., a receptor or ion channel. The subject assay enables rapid screening of large numbers of compounds to identify those which act as an agonist or antagonist to the bioactivity of the cellular protein. In this system, the cell is treated with a compound, and functional interaction of this compound with a cellular receptor yields a detectable signal, which can be specifically measured. The subject assays include methods of identifying compounds which specifically modulate, for example, heterologous receptors coupled to the pheromone response pathway in yeast. The subject assays are particularly amenable to the identification of specific agonists and antagonists of G protein-coupled receptors.

Abstract: Modified forms of G protein-coupled receptors which display altered ligand binding and/or coupling properties are provided as well as cells expressing such receptors and assays utilizing these cells for screening and identifying pharmaceutically effective compounds that specifically modulate the activity of a these modified forms of G protein coupled receptors. Yeast or mammalian cells can be used to express such receptors. The subject assays enable rapid screening of large numbers of compounds (e.g., compounds in a library) to identify those which are receptor agonists or antagonists. Compositions of matter, such as these novel receptors, novel recombinant yeast cells and novel gene constructs, are also provided. The instant assays provide a convenient format for discovering compounds which can be useful in modulating cellular function, as well as in understanding the pharmacology of compounds that specifically interact with these modified forms G protein coupled receptors.

Abstract: The present invention makes available a rapid, effective assay for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular receptor or ion channel. The subject assay enables rapid screening of large numbers of polypeptides in a library to identifying those polypeptides which induce or antagonize receptor bioactivity. The subject assay is particularly amenable for identifying surrogate ligands for orphan receptors.

Abstract: Yeast cells are engineered to express both a surrogate of a pheromone system protein (e.g., enzymes involved in maturation of ?-factor, transporters of a-factor, pheromone receptors, etc.) and a potential peptide modulator of the surrogate, in such a manner that the inhibition or activation of the surrogate affects a screenable or selectable trait of the yeast cells. Various additional features improve the signal-to-noise ratio of the screening/selection system.

Abstract: The present invention makes available a rapid, reproducible, robust assay system for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular protein, e.g., a receptor. or ion channel. The subject assay enables rapid screening of large numbers of compounds to identify those which act as an agonist or antagonist to the bioactivity of the cellular protein. In this system, the first cell is treated with a compound, and functional interaction of this compound with a cellular receptor yields a secreted signal. A second cell, bearing a receptor for this secreted signal, makes use of an indicator gene in a signaling pathway coupled to this second receptor. The subject assays include methods of identifying compounds which specifically modulate, for example, heterologous receptors coupled to the pheromone response pathway in yeast.

Abstract: Modified forms of G protein-coupled receptors which display altered ligand binding and/or coupling properties are provided as well as cells expressing such receptors and assays utilizing these cells for screening and identifying pharmaceutically effective compounds that specifically modulate the activity of a these modified forms of G protein coupled receptors. Yeast or mammalian cells can be used to express such receptors. The subject assays enable rapid screening of large numbers of compounds (e.g., compounds in a library) to identify those which are receptor agonists or antagonists. Compositions of matter, such as these novel receptors, novel recombinant yeast cells and novel gene constructs, are also provided. The instant assays provide a convenient format for discovering compounds which can be useful in modulating cellular function, as well as in understanding the pharmacology of compounds that specifically interact with these modified forms G protein coupled receptors.

Abstract: The present invention makes available a rapid, reproducible, robust assay system for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular protein, e.g., a receptor or ion channel. The subject assay enables rapid screening of large numbers of compounds to identify those which act as an agonist or antagonist to the bioactivity of the cellular protein. In particular, the assay of the invention makes use of a cell that harbors a protein that is responsive to a cellular signal transduction pathway. The protein is operatively linked to a polypeptide which causes a detectable signal to be generated upon stimulation of the pathway, e.g., when a compound interacts with and modulates the activity of a cellular receptor or ion channel of the cell.

Abstract: The present invention pertains to novel yeast cells which are useful for the expression of heterologous G protein coupled receptors. The yeast cells of the present invention can be used in screening assays which can be used to screen for modulators of G protein coupled receptors. Specifically, the invention provides novel yeast cells which express a heterologous G protein coupled receptor and mutant and/or chimeric G protein subunit molecules which serve to functionally integrate the heterologous into the pheromone signaling pathway of the yeast cell. The invention also provides for the expression of heterologous G protein coupled receptors which are functionally integrated into the yeast cell membrane using a yeast a factor leader sequence. Drug discovery assays using the subject yeast cells are also provided.

Abstract: The present invention pertains to novel yeast cells which are useful for the expression of heterologous G protein coupled receptors. The yeast cells of the present invention can be used in screening assays which can be used to screen for modulators of G protein coupled receptors. Specifically, the invention provides novel yeast cells which express a heterologous G protein coupled receptor and mutant and/or chimeric G protein subunit molecules which serve to functionally integrate the heterologous into the pheromone signaling pathway of the yeast cell. The invention also provides for the expression of heterologous G protein coupled receptors which are functionally integrated into the yeast cell membrane using a yeast ? factor leader sequence. Drug discovery assays using the subject yeast cells are also provided.

Abstract: Yeast cells are engineered to express both a surrogate of a pheromone system protein (e.g., enzymes involved in maturation of &agr;-factor, transporters of a-factor, pheromone receptors, etc.) and a potential peptide modulator of the surrogate, in such a manner that the inhibition or activation of the surrogate affects a screenable or selectable trait of the yeast cells. Various additional features improve the signal-to-noise ratio of the screening/selection system.

Abstract: The invention provides recombinant cells that have been engineered such that ligand stimulation of a receptor expressed by the cells leads to amplified signal transduction responses. In one embodiment, the receptor-expressing cells have been engineered to carry a heterologous DNA construct comprising a gene encoding a protein that activates the signal transduction pathway, which gene is operatively linked to a promoter that is responsive to activation of the signal transduction pathway. Stimulation of the receptor by a ligand leads to expression of the heterologous DNA construct encoding the protein that activates the signal transduction pathway such that signals generated by ligand binding to the receptor are amplified. Preferred cells are yeast cells expressing heterologous G protein coupled receptors functionally coupled to the yeast pheromone response pathway and overexpressing Ste5p, Ste4p, Ste12p, Ste11p or a dominant truncation allele of Ste20 via a pheromone-responsive promoter.

Abstract: The present invention makes available a rapid, reproducible, robust assay system for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular protein, e.g., a receptor or ion channel. The subject assay enables rapid screening of large numbers of compounds to identify those which act as an agonist or antagonist to the bioactivity of the cellular protein. In this system, the first cell is treated with a compound, and functional interaction of this compound with a cellular receptor yields a secreted signal. A second cell, bearing a receptor for this secreted signal, makes use of an indicator gene in a signaling pathway coupled to this second receptor. The subject assays include methods of identifying compounds which specifically modulate, for example, heterologous receptors coupled to the pheromone response pathway in yeast.