Nucleic acids encoding a G-protein coupled receptor involved in islet cell signaling
AssigneeMetabolex, Inc.
InventorsFrancine M. Gregoire, Jeffrey D. Johnson, John E. Blume
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Abstract
The invention provides isolated nucleic acid and amino acid sequences of human and murine islet cell G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, methods of screening for modulators of islet cell G-protein coupled receptors and methods of treating mammals with modulators of islet cell G-protein coupled receptor activity.
Claims66
An isolated nucleic acid encoding a G-protein coupled receptor, the receptor comprising greater than 70% amino acid identity to an amino acid sequence of SEQ ID NO:1, orSEQ ID NO:2.
An isolated nucleic acid encoding a G-protein coupled receptor, wherein the nucleic acid specifically hybridizes under highly stringent conditions to a nucleic acid having the sequence of SEQ ID NO:3, or SEQ ID NO:4.
An isolated nucleic acid encoding a G-protein coupled receptor, the receptor comprising greater than 70% amino acid identity to a polypeptide having a sequence of SEQ ID NO:1, or SEQ ID NO:2, wherein the nucleic acid selectively hybridizes under moderately stringent hybridization conditions to a nucleotide sequence of SEQ ID NO:3, or SEQ ID NO:4.
An isolated nucleic acid encoding an extracellular domain of a G-protein coupled receptor, the extracellular domain having greater than 70% amino acid sequence identity to the extracellular domain of SEQ ID NO:1.
An isolated nucleic acid encoding a transmembrane domain of a G-protein coupled receptor, the transmembrane domain comprising greater than 70% amino acid sequence identity to the transmembrane domain of SEQ ID NO:1.
An isolated G-protein coupled receptor, the receptor comprising greater than 70% amino acid sequence identity to an amino acid sequence of SEQ ID NO:1, or SEQ ID NO:2.
An isolated polypeptide comprising an extracellular domain of a G-protein coupled receptor, the extracellular domain comprising greater than 70% amino acid sequence identity to the extracellular domain of SEQ ID NO:1.
An isolated polypeptide comprising a transmembrane domain of a G-protein coupled receptor, the transmembrane domain comprising greater than 70% amino acid sequence identity to the transmembrane domain of SEQ ID NO:1.
A method for identifying a compound that modulates signaling in islet cells, the method comprising the steps of:
- (i) contacting the compound with a polypeptide comprising an extracellular domain of a G-protein coupled receptor, the extracellular domain comprising greater than 70% amino acid sequence identity to the extracellular domain of SEQ ID NO:1, or SEQ ID NO:2;
- and
- (ii) determining the functional effect of the compound upon the extracellular domain.
A method for identifying a compound that modulates signaling in islet cells, the method comprising the steps of:
- (i) contacting the compound with a polypeptide comprising a transmembrane domain of a G-protein coupled receptor, the transmembrane domain comprising greater than 70% amino acid sequence identity to the transmembrane domain of SEQ ID NO:1, or SEQ ID NO:2;
- and
- (ii) determining the functional effect of the compound upon the transmembrane domain.
A method of making a G-protein coupled receptor, the method comprising the step of expressing the receptor from a recombinant expression vector comprising a nucleic acid encoding the receptor, wherein the amino acid sequence of the receptor comprises greater than 70% amino acid identity to a polypeptide having a sequence of SEQ ID NO:1, or SEQ ID NO:2.
A method of making a recombinant cell comprising a G-protein coupled receptor, the method comprising the step of transducing the cell with an expression vector comprising a nucleic acid encoding the receptor, wherein the amino acid sequence of the receptor comprises greater than 70% amino acid identity to a polypeptide having a sequence of SEQ ID NO:1, or SEQ ID NO:2.
A method of making a recombinant expression vector comprising a nucleic acid encoding a G-protein coupled receptor, the method comprising the step of ligating to an expression vector a nucleic acid encoding the receptor, wherein the amino acid sequence of the receptor comprises greater than 70% amino acid identity to a polypeptide having a sequence of SEQ ID NO:1, or SEQ ID NO:2.
A method of diagnosing type I or type II diabetes or a predisposition for type I or type II diabetes in a patient, said method comprising:
- detecting the level of a polypeptide at least 70% identical to SEQ ID NOs:
- 1 or 2 in a sample from a patient, wherein a high level of the polypeptide in the sample, compared to level in a non-diabetic individual indicates that the patient is diabetic or is predisposed to some pathological aspects of diabetes.
A method of diagnosing type I or type II diabetes or a predisposition for type I or type II diabetes in a patient, said method comprising:
- detecting the level of activity of a polypeptide at least 70% identical to SEQ ID NOs:
- 1 or 2 in a sample from a patient, wherein a high level of activity of the polypeptide in the sample, compared to the level of activity in a non-diabetic individual indicates that the patient is diabetic or is predisposed to some pathological aspects of diabetes.
Dependencies are inferred from the claim text.