Rab small GTPase emerges as a regulator of TOR complex 2.

In diverse eukaryotic species from yeast to human, TOR (Target Of Rapamycin) protein kinase operates in signaling pathways that link extracellular stimuli to the control of cell growth and metabolism. TOR kinase functions in two distinct protein complexes, TOR complex 1 (TORC1) and 2 (TORC2). While TORC1 is known to be under the control of the Ras-like small GTPase Rheb, our knowledge about TORC2 regulation is very limited. We thus set out to identify TORC2 activators through genetic approaches in the fission yeast Schizosaccharomyces pombe. Here we briefly review our study that has identified a Rab-family GTPase, Ryh1 and its GEF (guanine nucleotide exchange factor) as positive regulators of TORC2 signaling in S. pombe. Considering the evolutionary conservation of the TOR pathways, it is conceivable that Rabfamily GTPases also play a role in the regulation of human TORC2 in cellular proliferation and insulin signaling.