Figure 8
A model for the interference of Akt with PtdIns4,5P2 and TORC2 signaling. In physiological conditions (a), regulatory complexes at the MCC/eisosomes and MCT/TORC2 microdomains regulate PM PtdIns4,5P2 and sphingolipid levels, respectively, in a coordinated way. PM Stress or lipid misbalance cause Slm1 to shift between compartments and bring Ypk1 in proximity to its activating kinases, turning on the TORC2 pathway. When mammalian p110α and Akt1 are co-expressed in yeast (b), PM pools of PtdIns4,5P2 are converted into PtdIns3,4,5P3 by PI3K activity, bringing Akt in proximity with PDK-like Pkh kinases and TORC2. Thus Akt takes over the role of Ypk short-circuiting TORC2 signaling and leading to enhanced PtdIns4,5P2 and phosphoinositide-dependent signaling for membrane growth inwards and actin-supported cell wall deposition. Artificial overproduction of Slm1 (c) leads to similar effects, probably by enhancing its presence at the MCT and biasing Ypk signaling towards a PtdIns4,5P2-dependent response uncoupled from physiological TORC2 modulation.
