Abstract: The present disclosure provides novel ?-arrestin-modulating compounds and methods of making and using same.

Abstract: Provided herein are compositions and methods for enhancing egress of T-cells from bone marrow of a subject in need thereof. Also provided are compositions and methods for the treatment of diseases characterized by reduced surface display of sphingosine-1-phosphate receptor 1 (S1P1), as well as methods of diagnosis/prognosis related to surface display of SIP 1. Methods of treating cancer are also provided.

Abstract: Disclosed are compositions and methods for modulating the ?-arrestin pathway selectively over the G protein pathway of a G protein couple receptor, such as parathyroid hormone receptor.

Abstract: The invention relates to a screening method for the Smoothened receptor for testing compositions as potential Smoothened receptor ligands, either agonist or antagonist activity, by use of an arrestin-reporter molecule conjugate. It also relates to testing cells and individuals by administering a smoothened receptor ligand-reporter molecule conjugate and observing locations where the ligand binds and then using an increased number of surface Smoothened receptors compared to a pre-established criteria as an indication of a cancerous growth or tumor.

Abstract: Disclosed are compositions and methods for modulating the ?-arrestin pathway selectively over the G protein pathway of a G protein couple receptor, such as parathyroid hormone receptor.

Abstract: The present invention relates to a modified arrestin which includes an arrestin molecule and a ubiquitin molecule. This modified arrestin has an increased affinity for a GPCR, and traffics with the GPCR into endosomes. The present invention further relates to a method of screening compounds and sample solutions for a GPCR agonist, antagonist, inverse agonist, or desensitization active compound. The modified arrestin is useful in the methods of the present invention.

Abstract: Desensitization of receptors that control disease is prevented by inhibiting G-protein receptor kinases. This has applicability, e.g., for patients with heart failure or on a left ventricular heart device or a heart pump after surgery or about to undergo surgery and at high risk for a cardiac event or on an opiate or addicted to opiate or with cystic fibrosis or rheumatoid arthritis.

Abstract: The present invention relates to methods of treating disease by altering G protein coupled receptor kinase (GRK) 6. This may be done by altering the expression or activity of the protein, for example. The present invention may be used for disease diagnosis, by detecting the expression or activity of GRK6. The present invention relates to a GRK6 deficient mouse, GRK6 splice variants, and methods of use. The present invention also relates to methods of identifying compounds that alter GRK6 activity. The present invention relates to disease treatment by altering GRK6 expression or activity.

Abstract: Disclosed is a transformed yeast cell containing a first heterologous DNA sequence which codes for a mammalian G protein-coupled receptor and a second heterologous DNA sequence which codes for a mammalian G protein ? subunit (mammalian G?). The first and second heterologous DNA sequences are capable of expression in the cell, but the cell is incapable of expressing an endogenous G protein ?-subunit (yeast G?). The cells are useful for screening compounds which affect the rate of dissociation of G? from G?? in a cell. Also disclosed is a novel DNA expression vector useful for making cells as described above. The vector contains a first segment comprising at least a fragment of the extreme amino-terminal coding sequence of a yeast G protein-coupled receptor. A second segment is positioned downstream from the first segment (and in correct reading frame therewith), with the second segment comprising a DNA sequence encoding a heterologous G protein-coupled receptor.