Ligand for G-protein coupled receptor FPRL2 and uses thereof
OwnerIsabelle Migeotte, Marc Parmentier +2inventors
InventorsIsabelle Migeotte, Marc Parmentier, David Communi, Maryse Brait
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Abstract
The present invention relates to methods, reagents and kits for detecting of formyl peptide receptor like-2 (FPRL2) polypeptide activity in a sample and identifying agents which modulate polypeptide activity. It further relates to antibodies raised against FPRL2. It further relates to substances for preventing, treating and/or alleviating diseases or disorders characterized by dysregulation of FPRL2 polypeptide signalling.
Claims39
A method for detecting a formyl peptide receptor-like 2 (FPRL2) polypeptide activity in a sample, comprising the steps of:
- a) incubating a sample comprising a formyl peptide receptor-like 2 (FPRL2) polypeptide with a heme binding protein (HBP) polypeptide under conditions which permit binding of said formyl peptide receptor like-2 (FPRL2) polypeptide and said heme binding protein (HBP) polypeptide;
- and
- b) detecting a second messenger,
- wherein said detection of said second messenger is indicative of the presence of said formyl peptide receptor like-2 (FPRL2) polypeptide activity in the sample.
A method for detecting a formyl peptide receptor-like 2 (FPRL2) polypeptide activity in a sample, comprising the steps of:
- a) incubating a first sample comprising formyl peptide receptor-like 2 (FPRL2) polypeptide with a heme binding protein (HBP) polypeptide under conditions which permit binding of said formyl peptide receptor like-2 (FPRL2) polypeptide and said heme binding protein (HBP) polypeptide;
- b) detecting a second messenger;
- c) incubating a second sample comprising said formyl peptide receptor like-2 (FPRL2) polypeptide in the absence of said heme binding protein (HBP) polypeptide under conditions which permit binding of said formyl peptide receptor like-2 (FPRL2) polypeptide and said heme binding protein (HBP) polypeptide;
- d) detecting a second messenger;
- and
- e) comparing said second messenger detected in step (b) with said second messenger detected in step (d), wherein a difference in said second messenger of step (b) relative to said second messenger of step (d) is indicative of said formyl peptide receptor-like 2 (FPRL2) polypeptide activity.
A method of identifying an agent that binds to a formyl peptide receptor like-2 (FPRL2) polypeptide, said method comprising:
- (a) contacting said formyl peptide receptor like-2 (FPRL2) polypeptide with a heme binding protein (HBP) polypeptide in the presence or absence of a candidate binding agent under conditions permitting binding of said heme binding protein (HBP) polypeptide to said formyl peptide receptor like-2 (FPRL2) polypeptide;
- and
- (b) measuring binding of said formyl peptide receptor like-2 (FPRL2) polypeptide to said heme binding protein (HBP) polypeptide, wherein a decrease in binding in the presence of said candidate binding agent, relative to binding in the absence of said candidate binding agent, identifies said candidate binding agent as an agent that binds to said formyl peptide receptor like-2 (FPRL2) polypeptide.
A method of identifying an agent that increases the signaling activity of a formyl peptide receptor like-2 (FPRL2) polypeptide, said method comprising:
- (a) contacting said formyl peptide receptor like-2 (FPRL2) polypeptide with an agent;
- (b) measuring a signaling activity of said formyl peptide receptor like-2 (FPRL2) polypeptide in the presence of said agent;
- and
- (c) comparing said activity measured in the presence of said agent to said activity measured in a reaction in which said formyl peptide receptor like-2 (FPRL2) polypeptide is contacted with a heme binding protein (HBP) polypeptide, wherein said agent is identified as an agonist that increases the signaling of said formyl peptide receptor like-2 (FPRL2) polypeptide when the amount of said activity measured in the presence of said agent is at least 10% of the amount induced by said heme binding protein (HBP) polypeptide.
A method of identifying an agent that decreases the signaling activity of formyl peptide receptor like-2 (FPRL2) polypeptide, said method comprising:
- (a) contacting said formyl peptide receptor like-2 (FPRL2) polypeptide with a heme binding protein (HBP) polypeptide in the presence or absence of an agent;
- (b) measuring a signaling activity of said formyl peptide receptor like-2 (FPRL2) polypeptide;
- (c) comparing the amount of the activity measured in a reaction comprising said formyl peptide like-2 (FPRL2) polypeptide and the heme binding protein (HBP) polypeptide without said agent to the amount of the activity measured in a reaction comprising said formyl peptide receptor like-2 (FPRL2) polypeptide, said heme binding protein (HBP) polypeptide and said agent, wherein a decrease in the activity in the presence of said agent relative to the activity in the absence of said agent identifies said agent as an antagonist or inverse agonist for said formyl peptide receptor like-2 (FPRL2) polypeptide.
An antibody which specifically reacts with formyl peptide receptor like-2 (FPRL2) polypeptide and which increases or decreases the binding of a heme binding protein (HBP) polypeptide to said formyl peptide receptor like-2 (FPRL2) polypeptide.
An antibody which specifically reacts with a formyl peptide receptor like-2 (FPRL2) polypeptide and which increases or decreases the signaling activity of a heme binding protein (HBP) polypeptide bound to said formyl peptide receptor like-2 (FPRL2) polypeptide.
A method of in vitro diagnosing a disease or disorder characterized by dysregulation of a formyl peptide receptor like-2 (FPRL2) polypeptide signaling, the method comprising:
- a) contacting a tissue sample comprising a formyl peptide receptor like-2 (FPRL2) polypeptide with a heme binding protein (HBP) polypeptide;
- b) detecting binding of said heme binding protein (HBP) polypeptide to said tissue sample;
- and
- c) comparing said binding detected in step (b) with a standard, wherein a difference in binding relative to said standard is diagnostic of a disease or disorder characterized by dysregulation of said formyl peptide receptor like-2 (FPRL2) polypeptide signaling.
A method of in vitro diagnosing a disease or disorder characterized by dysregulation of formyl peptide receptor like-2 (FPRL2) polypeptide signaling, the method comprising:
- a) contacting a tissue sample comprising a formnyl peptide receptor like-2 (FPRL2) polypeptide with a heme binding protein (HBP) polypeptide;
- b) detecting a signaling activity of said formyl peptide receptor like-2 (FPRL2) polypeptide in said tissue sample;
- and
- c) comparing said signaling activity detected in step (b) with a standard, wherein a difference in signaling activity relative to said standard is diagnostic of a disease or disorder characterized by dysregulation of formyl peptide receptor like-2 (FPRL2) polypeptide signaling.
A kit comprising a formyl peptide receptor like-2 (FPRL2) polypeptide and a heme binding protein (HBP) polypeptide, and packaging materials therefore.
A heme binding protein (HBP) polypeptide corresponding to a sequence represented by SEQ ID NO:18.
A polypeptide which has least 50% identity to the sequence represented by SEQ ID NO:
- 18.
A polypeptide which is a functional fragment of a heme binding protein (HBP) polypeptide corresponding to the sequence represented by SEQ ID NO:
- 18.
An antibody which specifically reacts with a formyl peptide receptor like-2 (FPRL2) polypeptide, and which increases or decreases the signaling activity of the formyl peptide receptor like-2 (FPRL2) polypeptide.
A method of treating an individual with a diseases or disorders characterized by dysregulation of FPRL2 polypeptide signaling comprising administering a therapeutically effective dose of a modulator of a FPRL2 polypeptide.
Dependencies are inferred from the claim text.