The mandate of this proposal is to test the hypothesis that discrete structural motifs of the proto-oncogene, Vav, may significantly contribute to PRLr-Vav interaction, Vav function, and Vav nuclear import, using the PRL-dependent Nb2 T-cell model system. Specifically, three aims are proposed, including: (1) to identify the Vav domains necessary for PRLr-Vav interaction using mutant Vav and PRLr recombinants in in vitro binding assays and confirmed in vivo by transient co-transfection; (2) to examine the association of Vav structure with function in two independent model systems by the ability of mutant Vav expression constructs to mediate PRLr signaling; and, (3) to determine the functional role of intranuclear Vav in lymphocyte proliferation and to examine its mechanism of nuclear importation.
