BIG1 as a Potential Guanine Nucleotide Exchange Factor for Rheb

摘要

The original aim of this idea grant is to demonstrate whether BIG1 functions as a nucleotide exchange factor (GEF) for the Rheb small GTPase. This was very exciting and provocative hypothesis. We found that BIG1 has no GEF activity towards Rheb. Therefore, our experimental data do not support the original hypothesis. The finding is not surprising because research hypothesis often are disproved or modified by experimental results. However, we had made important progress on a related topic in a different direction. We have identified Sin1 as a novel component of TORC2 (TOR complex 2). We demonstrated that Sin1 is essential for TORC2 complex formation and kinase activity. We also established that TORC2 is the kinase responsible for phosphorylation of the hydrophobic site of AKT. This finding significantly advanced our understanding on the function and regulation of the mTOR pathway.