Regulation of TORC2 function and localization by Rab5 GTPases in Saccharomyces cerevisiae.

摘要: The evolutionarily conserved Target of Rapamycin (TOR) complex-2 (TORC2) is an essential regulator plasma membrane homeostasis in budding yeast (Saccharomyces cerevisiae). In this yeast, TORC2 phosphorylates and activates the effector protein kinase Ypk1 its paralog Ypk2. These kinases, turn, carry out all crucial functions by phosphorylating thereby controlling activity at least a dozen downstream substrates. A previously uncharacterized interplay between Rab5 GTPases signaling was uncovered through analysis newly suspected target. Muk1, one two guanine nucleotide exchange factors for GTPases, found to be physiologically relevant substrate; and, genetic indicates that Ypk1-mediated phosphorylation Muk1. Second, it demonstrated both vivo vitro GTP-bound state GTPase Vps21/Ypt51 physically associates with acts as direct positive required full activity. interrelationships provide self-reinforcing control circuit sustained up-regulation TORC2-Ypk1 signaling. overview, we summarize experimental basis these findings, their implications, speculate molecular Rab5-mediated activation.