Syk is required for the activation of Akt survival pathway in B cells exposed to oxidative stress

Syk has been demonstrated to play a crucial role in oxidative stress signal ing in B cells. Here we report that Syk is required for the activation of t he phosphatidylinositol (PI) 3-kinase-Akt survival pathway in B cells expos ed to oxidative stress. Phosphorylation and activation of the serine-threon ine kinase Akt were markedly increased in B cells treated with H2O2. In Syk -deficient DT40 cells treated with low doses of H2O2 (10-100 mu M), Akt act ivation was considerably reduced. Pretreatment with wortmannin, a PI 3-kina se-specific inhibitor, completely blocked the Syk-dependent Akt activation. Following stimulation by low doses of H2O2, a significant increase in PI 3 -kinase activity was found in wild-type but not in Syk-deficient cells. The se findings suggest that PI 3-kinase mediates Syk-dependent Akt activation pathway, Furthermore, viability of Syk-deficient cells, after exposure to H 2O2, was dramatically decreased and caspase-9 activity was greatly increase d compared with that of the wild-type cells. These results suggest that Syk is essential for the Akt survival pathway in B cells and enhances cellular resistance to oxidative stress-induced apoptosis.