In this study we characterized the phosphorylation of tyrosine 311 and its role in the apoptotic function of PKC delta in glioma cells. We found that c-Abl phosphorylated PKC delta on tyrosine 311 in response to H2O2 and that this phosphorylation contributed to the apoptotic effect of H2O2. In contrast, Src, Lyn, and Yes were not involved in the phosphorylation of tyrosine 311 by H2O2. A phosphomimetic PKC delta mutant, in which tyrosine 311 was mutated to glutamic acid (PKC delta Y311E), induced a large degree of cell apoptosis. Overexpression of the PKC delta Y311E mutant induced the phosphorylation of p38 and inhibition of p38 abolished the apoptotic effect of the PKC delta mutant. These results suggest an important role of tyrosine 311 in the apoptotic function of PKC delta and implicate c-Abl as the kinase that phosphorylates this tyrosine. (c) 2006 Elsevier Inc. All rights reserved.