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Science 20 June 1997:
Vol. 276. no. 5320, pp. 1848 - 1850
DOI: 10.1126/science.276.5320.1848
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Reports

Transformation of Chicken Cells by the Gene Encoding the Catalytic Subunit of PI 3-Kinase

Hwai Wen Chang, Masahiro Aoki, David Fruman, Kurt R. Auger, Alfonso Bellacosa, Philip N. Tsichlis, Lewis C. Cantley, Thomas M. Roberts, Peter K. Vogt *

The avian sarcoma virus 16 (ASV 16) is a retrovirus that induces hemangiosarcomas in chickens. Analysis of the ASV 16 genome revealed that it encodes an oncogene that is derived from the cellular gene for the catalytic subunit of phosphoinositide 3-kinase (PI 3-kinase). The gene is referred to as v-p3k, and like its cellular counterpart c-p3k, it is a potent transforming gene in cultured chicken embryo fibroblasts (CEFs). The products of the viral and cellular p3k genes have PI 3-kinase activity. CEFs transformed with either gene showed elevated levels of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate and activation of Akt kinase.

H. W. Chang, M. Aoki, P. K. Vogt, Department of Molecular and Experimental Medicine, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
D. A. Fruman and L. C. Cantley, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Building HIM-1007, 330 Brookline Avenue, Boston, MA 02215, USA.
K. R. Auger and T. M. Roberts, Dana-Farber Cancer Institute, Mayer Building Room 854, 44 Binney Street, Boston, MA 02115, USA.
A. Bellacosa and P. N. Tsichlis, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
*   To whom correspondence should be addressed. E-mail: pkvogt{at}scripps.edu

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Akt Suppresses Apoptosis by Stimulating the Transactivation Potential of the RelA/p65 Subunit of NF-kappa B.
L. V. Madrid, C.-Y. Wang, D. C. Guttridge, A. J. G. Schottelius, A. S. Baldwin Jr., and M. W. Mayo (2000)
Mol. Cell. Biol. 20, 1626-1638
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The Catalytic Subunit of Phosphoinositide 3-Kinase: Requirements for Oncogenicity.
M. Aoki, C. Schetter, M. Himly, O. Batista, H. W. Chang, and P. K. Vogt (2000)
J. Biol. Chem. 275, 6267-6275
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Reentry into the Cell Cycle of Contact-inhibited Vascular Endothelial Cells by a Phosphatase Inhibitor. POSSIBLE INVOLVEMENT OF EXTRACELLULAR SIGNAL-REGULATED KINASE AND PHOSPHATIDYLINOSITOL 3-KINASE.
E. Suzuki, D. Nagata, M. Yoshizumi, M. Kakoki, A. Goto, M. Omata, and Y. Hirata (2000)
J. Biol. Chem. 275, 3637-3644
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The Phosphoinositide 3-OH Kinase/AKT2 Pathway as a Critical Target for Farnesyltransferase Inhibitor-Induced Apoptosis.
K. Jiang, D. Coppola, N. C. Crespo, S. V. Nicosia, A. D. Hamilton, S. M. Sebti, and J. Q. Cheng (2000)
Mol. Cell. Biol. 20, 139-148
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Expression Cloning of Protein Targets for 3-Phosphorylated Phosphoinositides.
V. R. Rao, M. N. Corradetti, J. Chen, J. Peng, J. Yuan, G. D. Prestwich, and J. S. Brugge (1999)
J. Biol. Chem. 274, 37893-37900
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A Random Walk in Oncogene Space: The Quest for Targets.
P. K. Vogt, M. Aoki, I. Bottoli, H.-W. Chang, S.-l. Fu, A. Hecht, J. S. Iacovoni, B.-H. Jiang, and U. Kruse (1999)
Cell Growth Differ. 10, 777-784
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Epstein-Barr virus envelope glycoprotein gp350 induces NF-{kappa}B activation and IL-1{beta} synthesis in human monocytes-macrophages involving PKC and PI3-K.
M. D’ADDARIO, A. AHMAD, J. W. XU, and J. MENEZES (1999)
FASEB J 13, 2203-2213
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Cellular survival: a play in three Akts.
S. R. Datta, A. Brunet, and M. E. Greenberg (1999)
Genes & Dev. 13, 2905-2927
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Heregulin Induces Phosphorylation of BRCA1 through Phosphatidylinositol 3-Kinase/AKT in Breast Cancer Cells.
S. Altiok, D. Batt, N. Altiok, A. Papautsky, J. Downward, T. M. Roberts, and H. Avraham (1999)
J. Biol. Chem. 274, 32274-32278
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Roles of Non-catalytic Subunits in Gbeta gamma -induced Activation of Class I Phosphoinositide 3-Kinase Isoforms beta and gamma.
U. Maier, A. Babich, and B. Nurnberg (1999)
J. Biol. Chem. 274, 29311-29317
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Allelic and locus heterogeneity in inherited venous malformations.
J. T. Calvert, T. J. Riney, C. D. Kontos, E. H. Cha, V. G. Prieto, C. R. Shea, J. N. Berg, N. C. Nevin, S. A. Simpson, K. A. Pasyk, et al. (1999)
Hum. Mol. Genet. 8, 1279-1289
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Transformation by v-Src: Ras-MAPK and PI3K-mTOR Mediate Parallel Pathways.
E. Penuel and G. S. Martin (1999)
Mol. Biol. Cell 10, 1693-1703
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Heparin-binding epidermal growth factor-like growth factor, a v-Jun target gene, induces oncogenic transformation.
S.-l. Fu, I. Bottoli, M. Goller, and P. K. Vogt (1999)
PNAS 96, 5716-5721
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Akt Protein Kinase Enhances Human Telomerase Activity through Phosphorylation of Telomerase Reverse Transcriptase Subunit.
S. S. Kang, T. Kwon, D. Y. Kwon, and S. I. Do (1999)
J. Biol. Chem. 274, 13085-13090
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Dedifferentiation of adenocarcinomas by activation of phosphatidylinositol 3-kinase.
M. Kobayashi, S. Nagata, T. Iwasaki, K. Yanagihara, I. Saitoh, Y. Karouji, S. Ihara, and Y. Fukui (1999)
PNAS 96, 4874-4879
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New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway.
L. C. Cantley and B. G. Neel (1999)
PNAS 96, 4240-4245
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Induction of Vascular Endothelial Growth Factor Expression in Endothelial Cells by Platelet-derived Growth Factor through the Activation of Phosphatidylinositol 3-Kinase.
D. Wang, H-J. S. Huang, A. Kazlauskas, and W. K. Cavenee (1999)
Cancer Res. 59, 1464-1472
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The Role of Phosphoinositide 3-Kinase Lipid Products in Cell Function.
L. E. Rameh and L. C. Cantley (1999)
J. Biol. Chem. 274, 8347-8350
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Molecular Mechanisms of Endothelin-1–Induced Cell-Cycle Progression : Involvement of Extracellular Signal-Regulated Kinase, Protein Kinase C, and Phosphatidylinositol 3-Kinase at Distinct Points.
E. Suzuki, D. Nagata, M. Kakoki, H. Hayakawa, A. Goto, M. Omata, and Y. Hirata (1999)
Circ. Res. 84, 611-619
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Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase Akt/protein kinase B.
B.-H. Jiang, M. Aoki, J. Z. Zheng, J. Li, and P. K. Vogt (1999)
PNAS 96, 2077-2081
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Cyclin D1 Expression Mediated by Phosphatidylinositol 3-Kinase through mTOR-p70S6K-Independent Signaling in Growth Factor-Stimulated NIH 3T3 Fibroblasts.
N. Takuwa, Y. Fukui, and Y. Takuwa (1999)
Mol. Cell. Biol. 19, 1346-1358
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