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AssigneeOregon Health & Science University
InventorsYoungman Oh, Ron G. Rosenfeld, Caroline K. Buckway
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There is disclosed novel mutant IGFBP-3 polypeptides and fragments thereof that have either no binding, or diminished binding to IGFs, yet retain their ability to bind to the human IGFBP-3 receptor (“P4.33”). The present invention provides novel mutant IGFBP-3 nucleic acid sequences, and expression systems. Additional exemplary embodiments provide for screening assays for identifying IGFBP-3 receptor antagonists or agonists, methods for modulating IGF-independent IGFBP-3 responses of cells expressing IGFBP-3 receptors, methods for inducing or potentiating apoptosis of cells expressing IGFBP-3 receptors, methods for treating solid tumors having cells expressing IGFBP-3 receptors, and compositions comprising polypeptides having either no binding, or diminished binding to IGFs, yet retain their ability to bind to the IGFBP-3 receptor.
An isolated nucleic acid comprising a sequence that encodes a polypeptide comprising an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID Nos:3-10, or of consecutive residues 54-87 thereof, wherein the polypeptide binds to the extracellular domain of the human IGFBP-3 receptor
A cultured cell comprising the expression vector of claim 6.
A purified polypeptide, the amino acid sequence of which comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID Nos:3-10, or of consecutive residues 54-87 thereof, wherein the polypeptide binds to the extracellular domain of the human IGFBP-3 receptor.
A method of identifying an IGFBP-3 receptor antagonist or agonist, the method comprising:
The method according to claim 15 wherein the detectable label is a radiolabel, a fluorescent reporter or quencher moiety, an enzymic label that catalyzes a colorometric or fluorometric change, or combinations thereof.
A method of identifying an IGFBP-3 receptor antagonist or agonist, the method comprising:
A method for modulating IGF-independent IGFBP-3 responses of a cell expressing a IGFBP-3 receptor, comprising contacting the cell with a polypeptide, the amino acid sequence of which comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID Nos:3-10, or of consecutive residues 54-87 thereof, wherein the polypeptide binds to the extracellular domain of the human IGFBP-3 receptor.
A method for inducing or potentiating apoptosis of a cell expressing a IGFBP-3 receptor, comprising contacting the cell with a polypeptide, the amino acid sequence of which comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID Nos:3-10, or of consecutive residues 54-87 thereof, wherein the polypeptide binds to the extracellular domain of the human IGFBP-3 receptor.
A method for treating a solid tumor having cells expressing a IGFBP-3 receptor, comprising contacting the cells with a polypeptide, the amino acid sequence of which comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID Nos:3-10, or of residues 54-87 thereof, wherein the polypeptide binds to the extracellular domain of the human IGFBP-3 receptor.
A composition comprising a polypeptide, the amino acid sequence of which comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID Nos:3-10, or of residues 54-87 thereof, wherein the polypeptide binds to the extracellular domain of the human IGFBP-3 receptor.
Dependencies are inferred from the claim text.