Figure 1.

Nonlinear signaling through the PI3K-Akt pathway. Growth factors activate receptor tyrosine kinases (RTKs) that further activate parallel growth pathways. The MAPK pathway, which signals via Ras and downstream effectors, is an example of a linear growth-promoting pathway. The PI3K-Akt pathway is an example of a nonlinear pathway that signals through protein and lipid effectors and through layers of oncoproteins (red) and growth suppressors (blue). Negative feedback loops of the PI3K-Akt pathway are shown in green (repressing) or orange (activating). The effectors of the pathway whose alterations show combinatorial additive effects with PTEN inactivation in cancers are encircled.