Figure 2

Overview of the two mammalian targets of rapamycin (mTOR) complexes and their potential regulation by the polycystins. A. Schematic overview of the composition of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) and cross-talk between them. mTORC1 contains mTOR, raptor, GβL/mLST, PRAS40 and DEP domains interactor of mTOR (DEPTOR). It can be regulated by a variety of activating or inhibitory cascades, as well as by amino acids capable of associating with Rag-GTP, leading to its association with mTORC1 to enhance its activity. One of the effectors of mTORC1, S6K1/2, regulates a negative feed-back loop at several levels. It is able to regulate insulin signalling by phosphorylating and inducing the degradation of IRS [111–113], and PDGF signalling by regulation of PDGF receptor levels [110]. In addition, S6K1/2 can phosphorylate rictor [114]. mTORC2 contains mTOR, Rictor, GβL/mLST, mSin and Protor. mTORC2 can phosphorylate Akt at Serine 473, regulating its specificity towards different substrates. Akt, in turn, can phosphorylate Tuberin (TSC2), potentially placing mTORC1 downstream of mTORC2 (see text). mTORC2 can also phosphorylate SGK1. B. Schematic representation of the effect of PC-1 on the two mTOR complexes. PC-1 has been described to inhibit the mTORC1 complex [87] whereas mTORC2 seems to be upregulated, since Akt phosphorylation at Serine 473 is enhanced by overexpression of PC-1 [70, 81]. The role of PC-2 in the regulation of these cascades and their precise mechanism of regulation remain to be clarified.