Protein kinase C-α overexpression stimulates Akt activity and suppresses apoptosis induced by interleukin 3 withdrawal

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Abstract
To investigate the role of protein kinase C (PKC) in apoptotic signaling induced by cytokine withdrawal, we expressed PKC-α, -δ and -ε individually in the 32D myeloid progenitor cells. The parental and PKC-δ- and PKC-ε- transfected 32D cells underwent apoptosis within 24 h in the absence of interleukin 3. In contrast, expression of PKC-α inhibited the onset of apoptosis as determined by genomic DNA fragmentation and flow cytometric analysis. Correlating with the inhibition of apoptosis, PKC-α transfectants exhibited increased activity of the endogenous Akt serine/threonine kinase. Furthermore, PKC-α, but not PKC-δ or -ε, specifically activated overexpressed Akt. PKC-α-induced Akt activity was partially dependent on phosphoinositol 3′ kinase (PI 3′K) since a PI 3′K inhibitor was able to suppress PKC-α-induced Akt activation. Both basal and interleukin 3-stimulated phosphorylation of Akt on serine 473 was enhanced in the PKC-α and Akt contransfectants. Coexpression of wild type Akt and PKC-α resulted in greater suppression of apoptosis than PKC-α expression alone. Together, our results demonstrate that suppression of apoptosis by PKC-α correlates with its ability of activating endogenous Akt. Furthermore, activation of overexpressed Akt by PKC-α is consistent with their synergistic effect on suppressing apoptosis, providing the strong evidence of cross talk between Akt and PKC-α.