Abstract: A method for identifying regulators of integrin activation by establishing a selected cell line which contains a functional integrin and a chimeric polypeptide having a cytoplasmic domain of an integrin subunit fused to a polypeptide containing extracellular and transmembrane domains that are not functional integrin domains, so that chimera can inhibit signaling activities of the functional integrin by interaction with integrin regulator molecules in the cytoplasm; transfecting the cell line with a selected cDNA expression library; expressing proteins of the cDNA expression library; and identifying proteins which when overexpressed overcome the inhibition of signaling activities by said chimeric polypeptide, said proteins being regulators of integrin. Methods of designing drugs to modify integrin function and cell lines for screening regulators of integrin activation are also provided.