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  • Oncogenomics
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Oncogenic transformation induced by membrane-targeted Akt2 and Akt3

Oncogene volume 20, pages 4419–4423 (2001)Cite this article

Abstract

The kinases Akt2, Akt3 and their myristylated variants, Myr-Akt2 and Myr-Akt3 were expressed by the RCAS vector in chicken embryo fibroblasts (CEF). Myr-Akt2 and Myr-Akt3 were strongly oncogenic, inducing multilayered foci of transformed cells. In contrast, wild-type Akt2 and Akt3 were only poorly transforming, their efficiencies of focus formation were more than 100-fold lower; foci appeared later and showed less multilayering. Addition of the myristylation signal not only enhanced oncogenic potential but also increased kinase activities. Myr-Akt2 and Myr-Akt3 also induced hemangiosarcomas in the animal, whereas wild type Akt2 and Akt3 were not oncogenic in vivo. Furthermore, Akt2, driven by the lck (lymphocyte specific kinase) promoter in transgenic mice, induced lymphomas. The oncogenic effects of Akt2 and Akt3 described here are indistinguishable from those of Akt1. The downstream targets relevant to oncogenic transformation are therefore probably shared by the three Akt kinases.

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References

  • Abraham KM, Levin SD, Marth JD, Forbush KA, Perlmutter RM . 1991 Proc. Natl. Acad. Sci. USA 88: 3977–3981

  • Alessi DR, Cohen P . 1998 Curr. Opin. Genet. Dev. 8: 55–62

  • Alessi DR, Downes CP . 1998 Biochim. Biophys. Acta 1436: 151–164

  • Ali IU, Schrimi LM, Dean M . 1999 J. Natl. Cancer Inst. 91: 1922–1932

  • Altomare DA, Lyons GE, Mitsuuchi Y, Cheng JQ, Testa JR . 1998 Oncogene 16: 2407–2411

  • Andersson S, Davis DL, Dahlback H, Jornvall H, Russell DW . 1989 J. Biol. Chem. 264: 8222–8229

  • Aoki M, Batista O, Bellacosa A, Tsichlis P, Vogt PK . 1998 Proc. Natl. Acad. Sci. USA 95: 14950–14955

  • Aoki M, Blazek E, Vogt PK . 2001 Proc. Natl. Acad. Sci. USA 98: 136–141

  • Aoki M, Schetter C, Himly M, Batista O, Chang HW, Vogt PK . 2000 J. Biol. Chem. 275: 6267–6275

  • Bellacosa A, de Feo D, Godwin AK, Bell DW, Cheng JQ, Altomare DA, Wan M, Dubeau L, Scambia G, Masciullo V et al . 1995 Int. J. Cancer 64: 280–285

  • Bellacosa A, Testa JR, Staal SP, Tsichlis PN . 1991 Science 254: 274–277

  • Brodbeck D, Cron P, Hemmings BA . 1999 J. Biol. Chem. 274: 9133–9136

  • Cantley LC, Neel BG . 1999 Proc. Natl. Acad. Sci. USA 96: 4240–4245

  • Ceci JD, Kovatch RM, Swing DA, Jones JM, Snow CM, Rosenberg MP, Jenkins NA, Copeland NG, Meisler MH . 1991 Oncogene 6: 323–332

  • Ceci JD, Siracusa LD, Jenkins NA, Copeland NG . 1989 Genomics 5: 699–709

  • Chan TO, Rittenhouse SE, Tsichlis PN . 1999 Ann. Rev. Biochem. 68: 965–1014

  • Chang HW, Aoki M, Fruman D, Auger KR, Bellacosa A, Tsichlis PN, Cantley LC, Roberts TM, Vogt PK . 1997 Science 276: 1848–1850

  • Cheng JQ, Altomare DA, Klein MA, Lee WC, Kruh GD, Lissy NA, Testa JR . 1997 Oncogene 14: 2793–2801

  • Cheng JQ, Godwin AK, Bellacosa A, Taguchi T, Franke TF, Hamilton TC, Tsichlis PN, Testa JR . 1992 Proc. Natl. Acad. Sci. USA 89: 9267–9271

  • Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK, Testa JR . 1996 Proc. Natl. Acad. Sci. USA 93: 3636–3641

  • Coffer PJ, Jin J, Woodgett JR . 1998 Biochem. J. 335: 1–13

  • Datta SR, Brunet A, Greenberg ME . 1999 Genes Dev. 13: 2905–2927

  • Di Cristofano A, Pandolfi PP . 2000 Cell 100: 387–390

  • Dufner A, Andjelkovic M, Burgering BM, Hemmings BA, Thomas G . 1999 Mol. Cell. Biol. 19: 4525–4534

  • Fruman DA, Meyers RE, Cantley LC . 1998 Ann. Rev. Biochem. 67: 481–507

  • Fukui Y, Hanafusa H . 1989 Mol. Cell. Biol. 9: 1651–1658

  • Hu P, Margolis B, Skolnik EY, Lammers R, Ullrich A, Schlessinger J . 1992 Mol. Cell. Biol. 12: 981–990

  • Hughes SH, Greenhouse JJ, Petropoulos CJ, Sutrave P . 1987 J. Virol. 61: 3004–3012

  • Konishi H, Kuroda S, Tanaka M, Matsuzaki H, Ono Y, Kameyama K, Haga T, Kikkawa U . 1995 Biochem. Biophys. Res. Commun. 216: 526–534

  • Liu AX, Testa JR, Hamilton TC, Jove R, Nicosia SV, Cheng JQ . 1998 Cancer Res. 58: 2973–2977

  • Maehama T, Dixon JE . 1999 Trends Cell. Biol. 9: 125–128

  • Masure S, Haefner B, Wesselink JJ, Hoefnagel E, Mortier E, Verhasselt P, Tuytelaars A, Gordon R, Richardson A . 1999 Eur. J. Biochem. 265: 353–360

  • Meier R, Alessi DR, Cron P, Andjelkovic M, Hemmings BA . 1997 J. Biol. Chem. 272: 30491–30497

  • Miwa W, Yasuda J, Murakami Y, Yashima K, Sugano K, Sekine T, Kono A, Egawa S, Yamaguchi K, Hayashiazaki Y, Sekiya T . 1996 Biochem. Biophys. Res. Commun. 225: 968–974

  • Nakatani K, Sakaue H, Thompson DA, Weigel RJ, Roth RA . 1999a Biochem. Biophys. Res. Commun. 257: 906–910

  • Nakatani K, Thompson DA, Barthel A, Sakaue H, Liu W, Weigel RJ, Roth RA . 1999b J. Biol. Chem. 274: 21528–21532

  • Osborn L, Rosenberg MP, Keller SA, Meisler MH . 1987 Mol. Cell. Biol. 7: 326–334

  • Peles E, Lamprecht R, Ben-Levy R, Tzahar E, Yarden Y . 1992 J. Biol. Chem. 267: 12266–12274

  • Reith AD, Ellis C, Lyman SD, Anderson DM, Williams DE, Bernstein A, Pawson T . 1991 EMBO J. 10: 2451–2459

  • Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ, Waterfield MD, Downward J . 1994 Nature 370: 527–532

  • Rodriguez-Viciana P, Warne PH, Vanhaesebroeck B, Waterfield MD, Downward J . 1996 EMBO J. 15: 2442–2451

  • Ruggeri BA, Huang L, Wood M, Cheng JQ, Testa JR . 1998 Mol. Carcinog. 21: 81–86

  • Shayesteh L, Lu Y, Kuo WL, Baldocchi R, Godfrey T, Collins C, Pinkel D, Powell B, Mills GB, Gray JW . 1999 Nat. Genet. 21: 99–102

  • Shepherd PR, Withers DJ, Siddle K . 1998 Biochem. J. 333: 471–490

  • Siracusa LD, Russell LB, Jenkins NA, Copeland NG . 1987 Genetics 117: 85–92

  • Staal SP . 1987 Proc. Natl. Aad. Sci. USA 84: 5034–5037

  • Whitman M, Kaplan DR, Schaffhausen B, Cantley L, Roberts TM . 1985 Nature 315: 239–242

  • Wymann MP, Pirola L . 1998 Biochim. Biophys. Acta 1436: 127–150

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Acknowledgements

Supported by US Public Health Service Research Grants CA 78230, CA 42564 and CA 79616. Douglas Geerdes and Jeffery Ludwig provided valuable technical assistance. We thank Dr Ushio Kikkawa for generously providing the akt3 construct. This is manuscript number 13437 of the Department of Molecular and Experimental Medicine, The Scripps Research Institute.

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  1. Ines Mende

    Present address: Universitatsklinikum Essen, Virchowstrasse 173, Essen, 45122, Germany

Authors and Affiliations

  1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, 92037, California CA, USA

    Ines Mende, Peter K Vogt & Masahiro Aoki

  2. Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania PA, USA

    Scott Malstrom & Philip N Tsichlis

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Mende, I., Malstrom, S., Tsichlis, P. et al. Oncogenic transformation induced by membrane-targeted Akt2 and Akt3. Oncogene 20, 4419–4423 (2001). https://doi.org/10.1038/sj.onc.1204486

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