Neuregulin/erbb signaling and integrin
AssigneeThe Regents of the University of California
InventorYoshikazu Takada
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Abstract
The present invention resides in the discovery that the specific interaction between neuregulin 1 (NRG1) and integrin is important for ErbB signaling, which in turn plays an important role in cellular signaling in various physiological processes such as cell proliferation, especially in cancer cells overexpressing ErbB family members. Thus, this invention provides for a novel method for inhibiting ErbB signaling by using an inhibitor of NRG1-integrin binding. A method for identifying inhibitors of NRG1-integrin binding is also described. Further disclosed are polypeptides, nucleic acids, and corresponding compositions for inhibiting ErbB signaling.
Claims45
A method for inhibiting proliferation of a cell, comprising the step of contacting the cell with an effective amount of an inhibitor of neuregulin-integrin binding.
A method for identifying an inhibitor of neuregulin-integrin binding, comprising the steps of
- (1) contacting an integrin and a polypeptide comprising an integrin-binding sequence of a neuregulin, in the presence of a test compound, under conditions permissible for neuregulin-integrin binding;
- and
- (2) detecting the level of polypeptide-integrin binding, wherein a decrease in the level of binding when compared with the level of binding in the absence of the test compound indicates the compound as an inhibitor of neuregulin-integrin binding.
An isolated polypeptide comprising a core amino acid sequence corresponding to residues 197-241 of SEQ ID NO:4 or residues 197-246 of SEQ ID NO:8, wherein, if the polypeptide comprises an additional amino acid sequence, the additional amino acid sequence does not comprise a sequence corresponding to residues 181-187 of SEQ ID NO:4 or 8, and wherein the polypeptide inhibits neuregulin-integrin binding.
A kit for identifying an inhibitor of neuregulin-integrin binding, comprising an integrin and a polypeptide comprising an integrin-binding sequence of a neuregulin.
Dependencies are inferred from the claim text.