Amphiregulin Regulates Phagocytosis-Induced Cell Death in Monocytes via EGFR and the Bcl-2 Protein Family

Figure 6

Schematic diagram displaying the impact of AREG on intrinsic apoptosis signaling. Phagocytosis of bacterial pathogens leads to the release of cytochrome c from the mitochondria through the mitochondrial apoptosis-induced channel (MAC), which is formed by the proteins Bax and Bak. In complex with Apaf-1, the released cytochrome c forms the apoptosome, which finally activates caspase-3 through binding and activation of caspase-9. Caspase-3 finally leads to the initiation of apoptosis. The signaling pathway can be inhibited by AREG-mediated activation of the EGF receptor. Binding of the cytokine AREG leads to an EGFR-mediated activation of the PI3K/Akt and MAPK/ERK pathway, which results in the phosphorylation of the protein BAD. In consequence, the heterodimers of BAD/Bcl-X_L and/or BAD/Bcl-2 dissociate, thereby enabling Bcl-2 and Bcl-X_L to inhibit Bax-induced apoptosis.