Figure 6
From: Molecular mechanisms mediating the G protein-coupled receptor regulation of cell cycle progression
Activation of PI3K-dependent cell cycle regulation. The expression, stability and activity of cyclins and CDK inhibitors are regulated by the activity of several PI3K-dependent pathways. Numerous GPCRs activate PI3K isoforms either through Gβγ subunits or via RTK and integrin transactivation. PI3Ks activate ERKs and Akt, leading to the transcriptional regulation of p27Kip1. In addition, Akt phosphorylates p27Kip1, thereby affecting its nuclear localization. Acting through TSC1, TSC2 and mTOR, Akt can negatively affect the stability of p27Kip1, although GPCR regulation of proliferation through mTOR has not been established (indicated by dashed lines). PI3Ks may also promote proliferation by promoting cyclin expression (via p70S6K) and stability (via Akt and GSK3). Dashed lines also identify the probable involvement of multiple, unidentified intermediates in the transcriptional regulation of cell cycle proteins.