Myeloid differentiation factor 2 (MD2) signaling and modulation
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 Myeloid Differentiation factor 2 (MD2) and integrin, especially integrin αvβ3, is involved in cellular signaling mediated by MD2-integrin, such as inflammatory response including sepsis. Thus, this invention provides for a novel method for inhibiting integrin signaling by using an inhibitor of MD2-integrin binding, such as a dominant negative mutant of MD2 without integrin-binding capability. A method for identifying inhibitors of MD2-integrin binding is also described. Further disclosed are polypeptides, nucleic acids, host cells, and corresponding compositions for inhibiting MD2-integrin signaling.
Claims20
An isolated peptide comprising SEQ ID NO:1 with at least one substitution at residue 20 or 39, wherein the peptide has decreased binding to integrin αvβ3 compared with SEQ ID NO:1.
A method for identifying an inhibitor of MD2-integrin αvβ3 binding, comprising the steps of
- (1) contacting integrin αvβ3 and a polypeptide, which consists of (i) the amino acid sequence of SEQ ID NO:
- 1 or (ii) the amino acid sequence of SEQ ID NO:1 and at least one heterologous amino acid sequence, in the presence of a test compound, under conditions permissible for MD2-integrin αvβ3 binding;
- and
- (2) detecting the level of polypeptide-integrin αvβ3 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 MD2-integrin αvβ3 binding.
Dependencies are inferred from the claim text.