This grant seeks to better understand the structure and function of protein tyrosine phosphatases (PTP), a superfamily of enzymes playing important roles in signal transduction. Our laboratory has identified a PTP-associated adapter protein in Drosophilia melanogaster known as Dock. Dock plays an essential role in axon guidance in the fly. We have isolated five Dock-associated proteins. We plan to clone and characterize these cDNAs and corresponding proteins in order to better understand their interactions with Dock, the PTP, as well as their roles in axonal guidance. Our goals also include the use of a novel strategy to identify substrates for two S. cerevisae phosphatases, ACR2 and YG4E. We anticipate that our strategies may be extended to understand the functions of other yeast phosphatases. Finally, our laboratory has solved the structure for the first phospholipase D supergene family member. The PLD supergene family members play key roles in signal transduction, vesicle traffic, mitosis, and bacterial pathogenesis. We plan to extend our structural and functional studies to other members of the PLD supergene family.