Methods and compositions for identifying receptor effectors

A method for identifying a modulator of a heterologous formyl peptide receptor like-1 (FPRL-1) receptor expressed by a cell, comprising:

• providing a recombinant cell comprising:
• a heterologous FPRL-1 receptor expressed in the cell membrane of said cell such that signal transduction activity via said receptor is modulated by interaction of an extracellular region of the receptor with an extracellular signal, said heterologous FPRL-1 receptor acting as a surrogate for an endogenous cell receptor in a signal transduction pathway of the cell;
• and
• a ligand agonist of said FPRL-1 receptor comprising a polypeptide or analog thereof, wherein said ligand agonist is transported to a location allowing interaction with the extracellular region of said FPRL-1 receptor expressed in the cell membrane, and is expressed at a level sufficient for said ligand agonist to bind to and activate said FPRL-1 receptor, thereby activating the signal transduction activity of said FPRL-1 receptor and generating a detectable signal;
• contacting said yeast cell with a test compound;
• and
• detecting an alteration in said signal generated by said ligand agonist to thereby identify a modulator of said receptor.

A method for identifying a modulator of a heterologous formyl peptide receptor like-1 (FPRL-1) receptor expressed by a cell, comprising:

• providing a recombinant cell comprising:
• a heterologous FPRL-1 receptor expressed in the cell membrane of said cell such that signal transduction activity via said receptor is modulated by interaction of an extracellular region of the receptor with an extracellular signal, said heterologous FPRL-1 receptor acting as a surrogate for an endogenous receptor in a signal transduction pathway of the cell;
• and
• a ligand agonist of said FPRL-1 receptor comprising a polypeptide or analog thereof, wherein said ligand agonist is transported to a location allowing interaction with the extracellular region of said FPRL-1 receptor expressed in the cell membrane, and is expressed at a level sufficient for said ligand agonist to bind to and activate said FPRL-1 receptor, thereby activating the signal transduction activity of said FPRL-1 receptor and generating a detectable signal;
• contacting said cell with each member of a library of test compounds;
• and
• detecting an alteration in said signal generated by said ligand agonist to thereby identify a modulator of said receptor.

A method for identifying a modulator of a heterologous formyl peptide receptor like-1 (FPRL-1) receptor expressed by a cell, comprising:

• providing a mixture of recombinant cells, each cell of which has a cell membrane and comprises:
• a heterologous formyl peptide receptor like-1 (FPRL-1) receptor expressed in the cell membrane of said cell such that signal transduction activity via said receptor is modulated by interaction of an extracellular region of the receptor with an extracellular signal, said heterologous FPRL-1 receptor acting as a surrogate for an endogenous cell receptor in a signal transduction pathway of the cell;
• a ligand agonist of said FPRL-1 receptor comprising a polypeptide or analog thereof, wherein said ligand agonist is transported to a location allowing interaction with the extracellular region of said FPRL-1 receptor expressed in the cell membrane, and is expressed at a level sufficient for said ligand agonist to bind to and activate said FPRL-1 receptor, thereby activating the signal transduction activity of said FPRL-1 receptor and generating a detectable signal;
• and
• a heterologous test polypeptide, wherein the heterologous test polypeptide is transported to a location allowing interaction with the extracellular region of said receptor expressed in the cell membrane;
• wherein collectively the mixture of cells expresses a library of said heterologous test polypeptides, said library being expressible at a sufficient level such that modulation of the signal transduction activity of said receptor by a heterologous test polypeptide within the library alters the detectable signal generated by said ligand agonist;
• and
• detecting an alteration in said signal generated by said ligand agonist to thereby identify a modulator of said receptor.

A method for identifying a modulator of a heterologous formyl peptide receptor like-1 (FPRL-1) receptor expressed by a cell, comprising:

• providing a first mixture of recombinant cells, each cell of which has a cell membrane and comprises:
• a heterologous formyl peptide receptor like-1 (FPRL-1) receptor expressed in the cell membrane of said cell such that signal transduction activity via said receptor is modulated by interaction of an extracellular region of the receptor with an extracellular signal, said heterologous FPRL-1 receptor acting as a surrogate for an endogenous cell receptor in a signal transduction pathway of the cell;
• and
• a ligand agonist of said FPRL-1 receptor comprising a polypeptide or analog thereof, wherein said ligand agonist is transported to a location allowing interaction with the extracellular region of said FPRL-1 receptor expressed in the cell membrane, and is expressed at a level sufficient for said ligand agonist to bind to and activate said FPRL-1 receptor, thereby activating the signal transduction activity of said FPRL-1 receptor and generating a detectable signal;
• contacting said first mixture with a second mixture of cells, wherein collectively the second mixture of cells expresses a library of heterologous test polypeptides that are transported to a location allowing interaction with the extracellular region of the FPRL-1 receptor expressed in the cell membrane of the cells of the first mixture;
• and
• detecting an alteration by a heterologous test polypeptide of said signal generated by said ligand agonist to thereby identify a modulator of said receptor.

A method for identifying a modulator of a heterologous formyl peptide receptor like-1 (FPRL-1) receptor expressed by a cell, comprising:

• providing a recombinant cell comprising a heterologous FPRL-1 receptor expressed in the cell membrane of said cell such that signal transduction activity via said receptor is modulated by interaction of an extracellular region of the receptor with an extracellular signal;
• and
• contacting said recombinant cell with a ligand agonist of said FPRL-1 receptor, said ligand agonist comprising a polypeptide, or analog thereof, to permit said ligand agonist to bind to and activate said FPRL-1 receptor, thereby activating the signal transduction activity of said FPRL-1 receptor and generating a detectable signal;
• contacting said cell with a test compound;
• and
• detecting an alteration in said signal generated by said ligand agonist to thereby identify a modulator of said receptor.

A method for identifying a modulator of a heterologous formyl peptide receptor like-1 (FPRL-1) receptor expressed by a cell, comprising:

• providing a first mixture of recombinant cells, each cell of which has a cell membrane and comprises:
• a heterologous FPRL-1 receptor expressed in the cell membrane of said cell such that signal transduction activity via said receptor is modulated by interaction of an extracellular region of the receptor with an extracellular signal, said heterologous FPRL-1 receptor acting as a surrogate for an endogenous cell receptor in a signal transduction pathway of the cell;
• and
• contacting said first mixture of recombinant cells with a ligand agonist of said FPRL-1 receptor comprising a polypeptide, or analog thereof, to permit said ligand agonist to bind to and activate said FPRL-1 receptor, thereby activating the signal transduction activity of said FPRL-1 receptor and generating a detectable signal;
• contacting said first mixture with a second mixture of cells, wherein collectively the second mixture of cells expresses a library of heterologous test polypeptides that are transported to a location allowing interaction with the extracellular region of the FPRL-1 receptor expressed in the cell membrane of the cells of the first mixture;
• and
• detecting an alteration in said signal generated by said ligand agonist to thereby identify a modulator of said receptor.