Abstract: Modulators of the immune system can be identified by determining the ability of candidate substances to affect the interaction of PKC-theta or a fragment thereof with its cognate. The interaction can be measured using binding of the cognate as an index, or can be measured using a physiological response.

Abstract: Improved methods for determining interactions between peptides or proteins and small molecules are disclosed. The invention methods can be used to screen libraries of either the small molecules or the proteins. In general, the methods comprise contacting an agent/ligand complex consisting essentially of an agent to be tested for binding to a target protein coupled to a ligand capable of binding a proteinaceous ligand-binding domain with a first fusion protein comprising said target protein and a first complementary portion of a segregable protein; and a second fusion protein comprising a proteinaceous ligand-binding domain and a second complementary portion of said segregable protein; and detecting whether the first complementary portion and second complementary portion are brought into proximity.

Abstract: Methods for assessing libraries of candidate modulators of intracellular signaling transmission pathways are described. The methods assess the ability of candidates from the library to inhibit the binding of peptides which represent participants in the signaling pathways as either a signal-generating protein or its cognate partner binding at a noncatalytic site. Specific peptides useful in this regard have been identified.

Abstract: The present invention discloses that the fyn protein binds to the PKC-theta protein. Based on this observation, the present invention provides methods of identifying agents which can be used to modulate immune system activity by blocking fyn/PKC-theta binding and therapeutic methods using such agents.