Abstract: Isoquinoline compounds with G are provided that influence, inhibit or reduce the action of a G-protein receptor kinase. Pharmaceutical compositions including therapeutically effective amounts of the isoquinoline compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, osteoporosis and glaucoma are also provided.

Abstract: The present invention is related to the detection of GPCR ligands in a test sample by using a single cell biosensor expressing a GPCR. Preferably, the test sample is derived from a biological or environmental sample. This invention may be used to detect the presence of a disease or to detect the presence of a harmful agent in the environment. Included in the present invention is an array of biosensors that detect ligands of various GPCRs.

Abstract: The present invention is related to the detection of GPCR ligands in a test sample by using a single cell biosensor expressing a GPCR. Preferably, the test sample is derived from a biological or environmental sample. This invention may be used to detect the presence of a disease or to detect the presence of a harmful agent in the environment. Included in the present invention is an array of biosensors that detect ligands of various GPCRs.

Abstract: The present invention relates to agonist-independent methods of screening for compounds that alter GPCR desensitization. Included in the present invention are cell lines containing GRKs, in which GPCRs are desensitized in the absence of agonist; the GRKs may be modified. The present invention relates to methods to determine if a GPCR is expressed at the plasma membrane, and if the GPCR has an affinity for arrestin. Modified GPCRs which have increased arrestin affinity are included in the present invention. These modified GPCRs are useful in methods to screen for compounds that alter desensitization, including both the agonist-independent methods and agonist-dependent methods described herein.

Abstract: The present invention relates to agonist-independent methods of screening for compounds that alter GPCR desensitization. Included in the present invention are cell lines containing GRKs, in which GPCRs are desensitized in the absence of agonist; the GRKs may be modified. The present invention relates to methods to determine if a GPCR is expressed at the plasma membrane, and if the GPCR has an affinity for arrestin. Modified GPCRs which have increased arrestin affinity are included in the present invention. These modified GPCRs are useful in methods to screen for compounds that alter desensitization, including both the agonist-independent methods and agonist-dependent methods described herein.

Abstract: The present invention is related to the detection of GPCR ligands in a test sample by using a single cell biosensor expressing a GPCR. Preferably, the test sample is derived from a biological or environmental sample. This invention may be used to detect the presence of a disease or to detect the presence of a harmful agent in the environment. Included in the present invention is an array of biosensors that detect ligands of various GPCRs.

Abstract: Isoquinoline compounds with G are provided that influence, inhibit or reduce the action of a G-protein receptor kinase. Pharmaceutical compositions including therapeutically effective amounts of the isoquinoline compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, osteoporosis and glaucoma are also provided.

Abstract: Isoquinoline compounds with G are provided that influence, inhibit or reduce the action of a G-protein receptor kinase. Pharmaceutical compositions including therapeutically effective amounts of the isoquinoline compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, osteoporosis and glaucoma are also provided.

Abstract: Methods of detecting G protein-coupled receptor (GPCR) activity in vitro and in vivo are provided. In one embodiment, the method includes providing at least one cell that expresses a GPCR and a plurality of conjugated proteins. Each of the plurality of conjugated proteins is formed by conjugating an arrestin protein and a detectable molecule. The plurality of conjugated proteins are substantially evenly distributed in the cytoplasm of the at least one cell. A first image of the at least one cell is obtained by detecting an amount of energy emitted from the detectable molecules and storing a value relative to the amount of energy. The at least one cell is treated with an agonist. A second image of the at least one cell is obtained. The first image and the second image are compared to detect the localization of at least some of the plurality of conjugated proteins at endocytic vesicles and/or endosomes.

Abstract: The present invention relates to agonist-independent methods of screening for compounds that alter GPCR desensitization. Included in the present invention are cell lines containing GRKs, in which GPCRs are desensitized in the absence of agonist; the GRKs may be modified. The present invention relates to methods to determine if a GPCR is expressed at the plasma membrane, and if the GPCR has an affinity for arrestin. Modified GPCRs which have increased arrestin affinity are included in the present invention. These modified GPCRs are useful in methods to screen for compounds that alter desensitization, including both the agonist-independent methods and agonist-dependent methods described herein.

Abstract: Described herein are methods of identifying a transmembrane receptor (TMR) agonist and compounds identified by this method. The TMR agonist (TMRA) is capable of activating TMR signaling while exhibiting reduced TMR internalization over a control compound.

Abstract: The present invention relates to modified G-protein coupled receptors (GPCRs). The modified GPCRs of the present invention include GPCRs that have been modified to have altered DRY motifs such that the modified GPCRs are constitutively desensitized. As such, the modified GPCRs of the present invention preferably localize to endocytic vesicles or endosomes in an agonist-independent manner. The invention also relates to methods of screening compounds and sample solutions for GPCR activity using the modified GPCRs.

Abstract: The present invention relates to modified G-protein coupled receptors (GPCRs). The modified GPCRs of the present invention include GPCRs that have been modified to have carboxyl terminal tails comprising one or more sites of phosphorylation, preferably one or more clusters of phosphorylation sites. The modified GPCRs of the present invention may comprise a retained portion of a carboxyl-terminus region from a first GPCR fused to a polypeptide, wherein the polypeptide comprises the one or more clusters of phosphorylation. The present invention also relates to methods of screening compounds and sample solutions for GPCR activity using the modified GPCRs.

Abstract: The methods of the present invention allow the screening of a test composition for non-receptor-specific GPCR desensitization inhibitory activity. The methods involve screening a test composition for an indication of GPCR desensitization inhibitory activity against two or more GPCRs that are different from each other. When there is an indication that a particular test composition has GPCR desensitization inhibitory activity with respect to each of the two or more GPCRs that are different from one another, then, according to the present invention, there is an indication that the test composition has non-receptor-specific GPCR desensitization inhibitory activity.

Abstract: The present invention relates to modified G-protein coupled receptors (GPCRs). The modified GPCRs of the present invention include GPCRs that have been modified to have carboxyl terminal tails comprising one or more sites of phosphorylation, preferably one or more clusters of phosphorylation sites. The modified GPCRs of the present invention may comprise a retained portion of a carboxyl-terminus region from a first GPCR fused to a polypeptide, wherein the polypeptide comprises the one or more clusters of phosphorylation. The present invention also relates to methods of screening compounds and sample solutions for GPCR activity using the modified GPCRs.

Abstract: The methods of the present invention allow the screening of a test composition for non-receptor-specific GPCR desensitization inhibitory activity. The methods involve screening a test composition for an indication of GPCR desensitization inhibitory activity against two or more GPCRs that are different from each other. When there is an indication that a particular test composition has GPCR desensitization inhibitory activity with respect to each of the two or more GPCRs that are different from one another, then, according to the present invention, there is an indication that the test composition has non-receptor-specific GPCR desensitization inhibitory activity.

Abstract: Methods of detecting G protein-coupled receptor (GPCR) activity in vitro and in vivo are provided. In one embodiment, the method includes providing at least one cell that expresses a GPCR and a plurality of conjugated proteins. Each of the plurality of conjugated proteins is formed by conjugating an arrestin protein and a detectable molecule. The plurality of conjugated proteins are substantially evenly distributed in the cytoplasm of the at least one cell. A first image of the at least one cell is obtained by detecting an amount of energy emitted from the detectable molecules and storing a value relative to the amount of energy. The at least one cell is treated with an agonist. A second image of the at least one cell is obtained. The first image and the second image are compared to detect the localization of at least some of the plurality of conjugated proteins at endocytic vesicles and/or endosomes.

Abstract: The present invention relates to modified G-protein coupled receptors (GPCRs). The modified GPCRs of the present invention include GPCRs that have been modified to have altered DRY motifs such that the modified GPCRs are constitutively desensitized. As such, the modified GPCRs of the present invention preferably localize to endocytic vesicles or endosomes in an agonist-independent manner. The invention also relates to methods of screening compounds and sample solutions for GPCR activity using the modified GPCRs.

Abstract: Methods of detecting G protein-coupled receptor (GPCR) activity in vitro and in vivo are provided. In one embodiment, the method includes providing at least one cell that expresses a GPCR and a plurality of conjugated proteins. Each of the plurality of conjugated proteins is formed by conjugating an arrestin protein and a detectable molecule. The plurality of conjugated proteins are substantially evenly distributed in the cytoplasm of the at least one cell. A first image of the at least one cell is obtained by detecting an amount of energy emitted from the detectable molecules and storing a value relative to the amount of energy. The at least one cell is treated with an agonist. A second image of the at least one cell is obtained. The first image and the second image are compared to detect the localization of at least some of the plurality of conjugated proteins at endocytic vesicles and/or endosomes.

Abstract: The present invention relates to modified G-protein coupled receptors (GPCRs). The modified GPCRs of the present invention include GPCRs that have been modified to have carboxyl terminal tails comprising one or more sites of phosphorylation, preferably one or more clusters of phosphorylation sites. The modified GPCRs of the present invention may comprise a retained portion of a carboxyl-terminus region from a first GPCR fused to a polypeptide, wherein the polypeptide comprises the one or more clusters of phosphorylation. The present invention also relates to methods of screening compounds and sample solutions for GPCR activity using the modified GPCRs.