University of California

Yoshikazu Takada

Yoko Takada

Seiji Mori

Masaaki Fujita

Jun Saegusa

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.

Myeloid differentiation factor 2 (MD2) signaling and modulation

The present invention provides dominant negative mutants of FGF2 for suppressing FGF-mediated cellular signaling. Related compositions, methods, and kits are disclosed.

Dominant-negative FGF2 antagonists

The present invention relates to the discovery that a secretory phospholipase A2 (sPLA2-IIA) plays an active role in mediating cellular signaling leading to an inflammatory response or cell proliferation by way of its specific binding with integrin &#x3b2; at site 2 of integrin &#x3b2;. More specifically, the invention provides a method for identifying inhibitors of inflammatory or proliferative signaling by screening for compounds that interrupt the specific binding of sPLA2 and integrin &#x3b2; at site 2. The invention also provides the novel use of a substance that suppresses the specific binding between sPLA2 and site 2 of integrin&#x3b2; for the purpose of treating or preventing a condition involving an undesired inflammatory response or cell proliferation.

Suppression of SPLA2-integrin binding for treating an inflammatory condition or suppressing cell proliferation

The invention relates to an isolated amino acid that can act as an antagonist to FGF signaling, comprising at least a portion of the FGF protein amino acid sequence, and including a mutation in either a) the integrin &#x3b1;v&#x3b2;3 binding region of FGF-1; or b) the FGFR binding region of FGF-1.

Compositions and methods related to anti-FGF agents

Interaction between insulin-like growth factor 1 (IGFI) and integrin is involved in integrin-mediated cellular signaling, such as enhanced proliferation of cells expressing integrins, especially integrin alpha v beta 3, alpha 6 beta. 1 and alpha 6. beta. 4. A method for inhibiting integrin signaling by using an inhibitor of IGFI-integrin binding is disclosed A method for identifying inhibitors of IGFI-integrin binding is also described. Further disclosed are polypeptides, nucleic acids, and corresponding compositions for inhibiting integrin signaling.

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Davis, CA, United States of America

Yoshikazu Takada