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.
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Abbreviations
- FCS:
-
fetal calf serum
- [3H]TdR:
-
[3H]thymidine
- HA:
-
hemagglutinin
- IL-3:
-
interleukin 3
- PH:
-
pleckstrin homology
- PI:
-
propidium iodide
- PI 3′K:
-
phosphoinositol 3′ kinase
- PKC:
-
protein kinase C
- SDS – PAGE:
-
sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- TPA:
-
12-O-tetradecanoylphorbol-13-acetate
- WT:
-
wild type
References
Ahmed NN, Grimes HL, Bellacosa A, Chan TO and Tsichlis PN. . 1997 Proc. Natl. Acad. Sci. USA 94: 3627–3632.
Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P and Hemmings BA. . 1996 EMBO J. 15: 6541–6551.
Andjelkovic M, Alessi DR, Meier R, Fernandez A, Lamb NJ, Frech M, Cron P, Cohen P, Lucocq JM and Hemmings BA. . 1997 J. Biol. Chem. 272: 31515–31524.
Barr LF, Campbell SE and Baylin SB. . 1997 Cell Growth Differ. 8: 381–392.
Bellacosa A, Testa JR, Staal SP and Tsichlis PN. . 1991 Science 254: 274–277.
Berra E, Municio M, Sanz L, Frutos S, Diaz-Meco M and Moscat J. . 1997 Mol. Cell. Biol. 17: 4346–4354.
Burgering BMT and Coffer PJ. . 1995 Nature 376: 599–602.
Cory S. . 1995 Annu. Rev. Immunol. 13: 513–543.
Datta K, Franke TF, Chan TO, Makris A, Yang S, Kaplan D, Morrison DK, Golemis EA and Tsichlis PN. . 1995 Mol. Cell. Biol. 15: 2304–2310.
Datta R, Kojima H, Yoshida K and Kufe D. . 1997 J. Biol. Chem. 272: 20317–20320.
del Peso L, Gonzalez-Garcia M, Page C, Herrera R and Nunez G. . 1997 Science 278: 687–689.
Diaz-Meco MT, Municio MM, Frutos S, Sanchez P, Lozano J, Sanz L and Moscat J. . 1996 Cell 86: 777–786.
Downward J. . 1998 Science 279: 673–674.
Emoto Y, Kisaki H, Manome Y, Kharbanda S and Kufe D. . 1996 Blood 87: 1990–1996.
Emoto Y, Manome Y, Meinhardt G, Kisaki H, Kharbanda S, Robertson M, Ghayur T, Wong WW, Kamen R, Weichselbaum R and Kufe D. . 1995 EMBO J. 14: 6148–6156.
Eves EM, Xiong W, Bellacosa A, Kennedy SG, Tsichlis PN, Rosner MR and Hay N. . 1998 Mol. Cell. Biol. 18: 2143–2152.
Fairbairn LJ, Cowling GJ, Reipert BM and Dexter TM. . 1993 Cell 74: 823–832.
Franke TF, Kaplan DR and Cantley LC. . 1997 Cell 88: 435–437.
Franke TF, Yang S, Chan TO, Datta K, Kazlauskas A, Morrison DK, Kaplan DR and Tsichlis PN. . 1995 Cell 81: 727–736.
Ghayur T, Hugunin M, Talanian R, Ratnofsky S, Quinlan C, Emoto Y, Pandey P, Datta R, Huang Y, Kharbanda S, Allen H, Kamen R, Wong W and Kufe D. . 1996 J. Exp. Med. 184: 2399–2404.
Hemming BA. . 1997 Science 277: 534.
Johannes F-J, Prestle J, Eis S, Oberhagemann P and Pfizenmaier K. . 1994 J. Biol. Chem. 269: 6140–6148.
Jones PF, Jakubowicz T, Pitossi FJ, Maurer F and Hemmings BA. . 1991 Proc. Natl. Acad. Sci. USA 88: 4171–4175.
Kauffmann-Zeh A, Rodriguez-Viciana P, Ulrich E, Gilbert C, Coffer P, Downward J and Evan G. . 1997 Nature 385: 544–548.
Kelly M, Tang Y, Rosensweig N, Clejan S and Beckman BS. . 1998 Blood 92: 416–424.
Kennedy SG, Wagner AJ, Conzen SD, Jordan J, Bellacosa A, Tsichlis PN and Hay N. . 1997 Genes Dev. 11: 701–713.
Korsmeyer SJ. . 1995 Trends Genet. 11: 101–105.
Le Good JA, Ziegler WH, Parekh DB, Alessi DR, Cohen P and Parker PJ. . 1998 Science 281: 2042–2045.
Li W, Yu J-C, Michieli P, Beeler JF, Ellmore N, Heidaran MA and Pierce JH. . 1994 Mol. Cell. Biol. 14: 6727–6735.
Li W, Yu J-C, Shin D-Y and Pierce JH. . 1995 J. Biol. Chem. 270: 8311–8318.
Mischak H, Pierce JH, Goodnight J, Kazanietz MG, Blumberg PM and Mushinski JF. . 1993 J. Biol. Chem. 268: 20110–20115.
Mizuno K, Noda K, Araki T, Imaoka T, Kobayashi Y, Akita Y, Shimonaka M, Kishi S and Ohno S. . 1997 Eur. J. Biochem. 250: 7–18.
Nishizuka Y. . 1992 Science 258: 607–614.
O'Brian C. . 1998 Oncology Reports 5: 305–309.
Ohno S, Akita Y, Hata A, Osada S-I, Kubo K, Konno Y, Akimoto K, Mizuno K, Saido T, Kuroki T and Suzuki K. . 1991 Adv. Enzyme Regul. 31: 287–303.
Peter ME, Heufelder AE and Hengartner MO. . 1997 Proc. Natl. Acad. Sci. USA 94: 12736–12737.
Pullen N, Dennis PB, Andjelkovic M, Dufner A, Kozma SC, Hemmings BA and Thomas G. . 1998 Science 279: 707–710.
Saini KS and Walker NI. . 1998 Mol. Cell. Biochem. 178: 9–25.
Songyang Z, Baltimore D, Cantley LC, Kaplan DR and Franke TF. . 1997 Proc. Natl. Acad. Sci. USA 94: 11345–11350.
Stephens L, Anderson K, Stokoe D, Erdjument-Bromage H, Painter GF, Holmes AB, Gaffney PRJ, Reese CB, McCormick F, Tempst P, Coadwell J and Hawkins PT. . 1998 Nature 279: 710–714.
Stokoe D, Stephens LR, Copeland T, Gaffney PR, Reese CB, Painter GF, Holmes AB, McCormick F and Hawkins PT. . 1997 Science 277: 567–570.
Valverde AM, Sinnett-Smith J, Van Lint J and Rozengurt E. . 1994 Proc. Natl. Acad. Sci. USA 91: 8572–8576.
Vanhaesebroeck B, Leevers SJ, Panayotou G and Waterfield MD. . 1997 Trends Biochem. Sci. 22: 267–272.
Whelan RD and Parker PJ. . 1998 Oncogene 16: 1939–1944.
Whitman SP, Civoli F and Daniel LW. . 1997 J. Biol. Chem. 272: 23481–23484.
Acknowledgements
We would like to thank Veena Kapoor for her excellent technical assistance for flow cytometric analysis.
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Li, W., Zhang, J., Flechner, L. et al. Protein kinase C-α overexpression stimulates Akt activity and suppresses apoptosis induced by interleukin 3 withdrawal. Oncogene 18, 6564–6572 (1999). https://doi.org/10.1038/sj.onc.1203065
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DOI: https://doi.org/10.1038/sj.onc.1203065
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