Abstract: The present invention relates to mammals into which foreign DNA has been introduced or in which various modifications or substitutions have been made to an integrin ? subunit, thereby generating transgenic or genetically-engineered non-human mammals. In particular, the present invention provides a transgenic mammal in which the endogenous GP IIIa gene has been replaced with an altered or mutant GP IIIa gene in which one or all of the phosphorylable cytoplasmic tyrosine residues have been replaced with non-tyrosine residues such as phenylalanine. Since the platelets in the blood of the resultant transgenic mammals expressing in wild-type mammals, these genetically-engineered animals provide a critical tool for assessing the importance of the phosphorylation reaction for platelet function. The invention is also useful for studying the effect of the mutant GP IIIa integrin subunit on biological processes other than platelet formation.

Abstract: The present invention discloses that phosphorylation of cytoplasmic tyrosine residues in the &bgr;-subunit of integrins is needed for signal protein association. The invention provides methods of identifying signaling partners involved in integrin mediated signaling, methods of identifying agents which block integrin mediated signaling, methods of using agents which block integrin mediated signaling to modulate biological and pathological processes, and agents which block integrin mediated signaling.

Abstract: The present invention discloses that phosphorylation of cytoplasmic tyrosine residues in the &bgr;-subunit of integrins is needed for signal protein association. The invention provides methods of identifying signaling partners involved in integrin mediated signaling, methods of identifying agents which block integrin mediated signaling, methods of using agents which block integrin mediated signaling to modulate biological and pathological processes, and agents which block integrin mediated signaling.