PPAR-𝛾 Agonists and Their Effects on IGF-I Receptor Signaling: Implications for Cancer

Figure 3

Cross-Talk between PPAR- 𝛾 and IGF system downstream signaling pathways . The points of interaction between PPAR-𝛾 and MAPK/PI3K pathways occur at different levels and are indicated as arrows (activation) or bars (inhibition). In some cell contexts PPAR-𝛾 ligands reduce MEK1/2 protein expression (A) and inhibit ERK1/2 phosphorylation (B). However, in other cell systems, PPAR-𝛾 agonists may activate ERK1/2 (C). Alternative mechanisms of interaction between PPAR-𝛾 and MAPK/PI3K pathways include (D) ERK-mediated PPAR-𝛾 phosphorylation at Ser84/114; (E) MEK1/2-dependent PPAR-𝛾 nuclear export followed by PPAR-𝛾 degradation; (F) PTEN upregulation; (G) mTOR downregulation via activation of AMPK; (H) inhibition of p70S6K phosphorylation.