The Vav family of signaling molecules is a multifaceted group of proteins that have been implicated in cancer, the immune response, cytoskeleton rearrangement and Ca2+ signaling. However, the roles these proteins have in vivo are not fully understood.
The aim of this proposal is to address the function of Vav in the genetic amenable model system Caenorhabditis elegans. C. elegans Vav, encoded by vav1, is widely expressed and is required for viability. Evidence thus far indicates that vav-1 function is required for normal pharyngeal function and viability. The first goal of this proposal is to analyze the structure and function of vav-1 during C. elegans development. This will entail a careful analysis of structural and physiological defects that arise in vav-1 mutants. Additionally, mutant and deletion constructs Will be generated and their function will be analyzed in the wild type and vav-1 mutant backgrounds. The second goal is to identify components that interact within the VAV-1 signaling pathway. This will be accomplished by conducting suppressor screens on vav-1 mutant phenotypes. Since there are many similarities between vertebrate and invertebrate signaling cascades and evidence points to their commonality at the molecular, structural and functional level, these approaches will identify possible downstream effectors of the Vav signaling pathways and will aid in elucidating the function of Vav in vivo.
| Norman, Kenneth R; Cordes, Shaun; Qadota, Hiroshi et al. (2007) UNC-97/PINCH is involved in the assembly of integrin cell adhesion complexes in Caenorhabditis elegans body wall muscle. Dev Biol 309:45-55 |
