SARA is a novel anchoring protein essential for TGF-ß signal transduction

grantor: University of TorontoIn this study, I identify a novel human gene, which is the homolog of a Xenopus gene. I present the molecular cloning and characterization of the protein product of this gene, which is, called SARA (S_mad A_nchor for R_eceptor A_ctivation). SARA is a novel component of the TGF-ß signal transduction pathway. It interacts directly with Smad2, a cytoplasmic mediator of TGF-ß signalling and functions to recruit Smad2 to specific subcellular sites of action. I also demonstrate that TGF-ß receptors localize to these regions in the cell and show a physical association of SARA with receptor complexes. I characterize the SARA domains required for proper subcellular localization and Smad2 interaction, and demonstrate that a mutant version of this protein blocks Smad2 signalling. Based on these characterizations, I propose that SARA functions to recruit Smad2 to the TGF-ß receptor by controlling its subcellular localization.M.Sc