β-Arrestin prevents cell apoptosis through pro-apoptotic ERK1/2 and p38 MAPKs and anti-apoptotic Akt pathways

Our previous studies have shown that beta-arrestin 2 plays an anti-apoptotic effect. However, the mechanisms by which beta-arrestin contribute to anti-apoptotic role remain unclear. In this study, we show that a deficiency of either beta-arrestin 1 or beta-arrestin 2 significantly increases serum deprivation (SD)-induced percentage of apoptotic cells. beta-arrestin 2 deficient-induced apoptosis was inhibited by transfection with beta-arrestin 2 full-length plasmid, revealing that SD-induced apoptosis is dependent on beta-arrestin 2. Furthermore, in the absence of either beta-arrestin 1 or beta-arrestin 2 significantly enhances SD-induced the level of pro-apoptotic proteins, including cleaved caspase-3, extracellular-signal regulated kinase 1/2 (ERK1/2) and p38, members of mitogen-activated protein kinases (MAPKs). In addition, a deficiency of either beta-arrestin 1 or beta-arrestin 2 inhibits phosphorylation of Akt. The SD-induced changes in cleaved caspase-3, ERK1/2 and p38 MAPKs, Akt, and apoptotic cell numbers could be blocked by double knockout of beta-arrestin 1/2. Our study thus demonstrates that beta-arrestin inhibits cell apoptosis through pro-apoptotic ERK1/2 and p38 MAPKs and anti-apoptotic Akt signaling pathways.