| Autor: |
Li W; Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland, MD 20892, USA., Zhang J, Flechner L, Hyun T, Yam A, Franke TF, Pierce JH |
| Jazyk: |
angličtina |
| Zdroj: |
Oncogene [Oncogene] 1999 Nov 11; Vol. 18 (47), pp. 6564-72. |
| DOI: |
10.1038/sj.onc.1203065 |
| Abstrakt: |
To investigate the role of protein kinase C (PKC) in apoptotic signaling induced by cytokine withdrawal, we expressed PKC-alpha, -delta and -epsilon individually in the 32D myeloid progenitor cells. The parental and PKC-delta- and PKC-epsilon-transfected 32D cells underwent apoptosis within 24 h in the absence of interleukin 3. In contrast, expression of PKC-alpha inhibited the onset of apoptosis as determined by genomic DNA fragmentation and flow cytometric analysis. Correlating with the inhibition of apoptosis, PKC-alpha transfectants exhibited increased activity of the endogenous Akt serine/threonine kinase. Furthermore, PKC-alpha, but not PKC-delta or -epsilon, specifically activated overexpressed Akt. PKC-alpha-induced Akt activity was partially dependent on phosphoinositol 3' kinase (PI 3'K) since a PI 3'K inhibitor was able to suppress PKC-alpha-induced Akt activation. Both basal and interleukin 3-stimulated phosphorylation of Akt on serine 473 was enhanced in the PKC-alpha and Akt contransfectants. Coexpression of wild type Akt and PKC-alpha resulted in greater suppression of apoptosis than PKC-alpha expression alone. Together, our results demonstrate that suppression of apoptosis by PKC-alpha correlates with its ability of activating endogenous Akt. Furthermore, activation of overexpressed Akt by PKC-alpha is consistent with their synergistic effect on suppressing apoptosis, providing the strong evidence of cross talk between Akt and PKC-alpha. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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