NIH Research Festival
Vav proteins function in an array of signaling pathways where they exhibit oncogenic potential. They have roles as GEFs, but also in adapter function independent of their GEF activity. Most PKCs are activated and translocate from the cytosol to the plasma membrane via DAG and phorbol esters binding to their C1 domain. The native C1 domain in Vav does not respond to phorbol esters. Mutations in 5 key amino acid residues in the C1 domain of Vav1 (Vav1 5x) have been shown to render it more PKC-like yielding a Vav1 protein sensitive to phorbol esters and able to translocate to the plasma membrane. A similar approach has been taken with Vav3. An evaluation of how binding of phorbol esters and the resultant localization to the plasma membrane influence Vav3 5x GEF activity and protein interactions will be presented. The mutations in Vav3 5x interfere with its ability to activate GTPases. The mutations do not interfere with most protein interactions; established protein interactions such as SRC, SHP2 and tubulin are detected with Vav3 5x as with Vav3 WT. The increase in association of Vav3 5x with the plasma membrane in response to phorbol esters results in an increase in some protein-protein interactions such as the plasma membrane associated PKCs. Targeting Vav3 to the plasma membrane by way of its C1 domain and changing its localization may change protein function. Such a technique may be useful as a therapeutic strategy and we are trying to understand possible implications of such an approach.
Scientific Focus Area: Cancer Biology
This page was last updated on Friday, March 26, 2021