P-selectin mutants and modulation of integrin-mediated signaling
AssigneeThe Regents of the University of California
InventorsYoshikazu Takada, Yoko Takada
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Abstract
The present invention resides in the discovery that the specific interaction between P-selectin (CD62P) and integrin, especially integrin αvβ3 and αIIbβ3, is involved in cellular signaling mediated by CD62P-integrin, such as inflammation and cancer metastasis. Thus, this invention provides for a novel method for inhibiting inflammation or cancer metastasis mediated by integrin signaling by using an inhibitor of CD62P-integrin binding, such as a dominant negative mutant of CD62P without integrin-binding capability. A method for identifying inhibitors of CD62P-integrin binding is also described. Further disclosed are polypeptides, nucleic acids, host cells, and corresponding compositions for inhibiting CD62P-integrin signaling.
Claims20
An isolated polypeptide comprising SEQ ID NO:1 with at least one mutation at residue 16, 17, 54, 55, 58, 66, 67, 84, 85, or 88, wherein the polypeptide has decreased binding to integrin αvβ3 or αIIbβ3 compared with SEQ ID NO:
- 1.
A method for identifying an inhibitor of CD62P-integrin αvβ3 or αIIbβ3 binding, comprising the steps of
- (1) contacting integrin αvβ3 or αIIbβ3 and a polypeptide comprising SEQ ID NO:
- 1, in the presence of a test compound, under conditions permissible for CD62P-integrin αvβ3 or αIIbβ3 binding;
- and
- (2) detecting the level of polypeptide-integrin αvβ3 or αIIbβ3 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 CD62P-integrin αvβ3 or αIIbβ3 binding.
Dependencies are inferred from the claim text.