REFERENCES
- Alessi, D. R., S. R. James, C. P. Downes, A. B. Holmes, P. R. Gaffney, C. B. Reese, and P. Cohen 1997. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα. Curr. Biol. 7: 261–269.
- Alessi, D. R., M. T. Kozlowski, Q.-P. Weng, N. Morrice, and J. Avruch 1998. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro. Cum. Biol. 8: 69–81.
- Andjelkovic, M., D. R. Alessi, R. Meier, A. Fernandez, N. J. Lamb, M. Frech, P. Cron, P. Cohen, J. M. Lucocq, and B. A. Hemmings 1997. Role of translocation in the activation and function of protein kinase B. J. Biol. Chem. 272: 31515–31524.
- Auger, K. R., L. A. Serunian, S. P. Soltoff, P. Libby, and L. C. Cantley 1989. PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells. Cell 57: 167–175.
- Baim, S. B., M. A. Labow, A. J. Levine, and T. Shenk 1991. A chimeric mammalian transactivator based on the lac repressor that is regulated by temperature and isopropyl beta-d-thiogalactopyranoside. Proc. Natl. Acad. Sci. USA 88: 5072–5076.
- Bellacosa, A., J. R. Testa, S. P. Staal, and P. N. Tsichlis 1991. A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region. Science 254: 274–277.
- Beretta, L., A. C. Gingras, Y. V. Svitkin, M. N. Hall, and N. Sonenberg 1996. Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. EMBO J. 15: 658–664.
- Brown, E. J., M. W. Albers, T. B. Shin, K. Ichikawa, C. T. Keith, W. S. Lane, and S. L. Schreiber 1994. A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature 369: 756–758.
- Burgering, B. M., and P. J. Coffer 1995. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature 376: 599–602 (Comment.)
- Cafferkey, R., P. R. Young, M. M. McLaughlin, D. J. Bergsma, Y. Koltin, G. M. Sathe, L. Faucette, W. K. Eng, R. K. Johnson, and G. P. Livi 1993. Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity. Mol. Cell. Biol. 13: 6012–6023.
- Cantley, L. C., K. R. Auger, C. Carpenter, B. Duckworth, A. Graziani, R. Kapeller, and S. Soltoff 1991. Oncogenes and signal transduction. Cell 64: 281–302 (Erratum, 65:914, 1991.)
- Carpenter, C. L., and L. C. Cantley 1996. Phosphoinositide kinases. Curr. Opin. Cell Biol. 8: 153–158.
- Chang, H. W., M. Aoki, D. Fruman, K. R. Auger, A. Bellacosa, P. N. Tsichlis, L. C. Cantley, T. M. Roberts, and P. K. Vogt 1997. Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase. Science 276: 1848–1850.
- Cheatham, B., C. J. Vlahos, L. Cheatham, L. Wang, J. Blenis, and C. R. Kahn 1994. Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol. Cell. Biol. 14: 4902–4911.
- Chung, J., T. C. Grammer, K. P. Lemon, A. Kazlauskas, and J. Blenis 1994. PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase. Nature 370: 71–75.
- Chung, J., C. J. Kuo, G. R. Crabtree, and J. Blenis 1992. Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. Cell 69: 1227–1236.
- Cichy, S., S. Uddin, A. Danilkovich, S. Guo, A. Klippel, and T. G. Unterman 1998. Protein kinase B/Akt mediates the effects of insulin and phosphatidylinositol 3-kinase on basal hepatic IGFBP-1 gene expression through a conserved insulin response sequence. J. Biol. Chem. 273: 6482–6487.
- Derijard, B., M. Hibi, I. H. Wu, T. Barrett, B. Su, T. Deng, M. Karin, and R. J. Davis 1994. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76: 1025–1037.
- Didichenko, S. A., B. Tilton, B. A. Hemmings, K. Ballmer-Hofer, and M. Thelen 1996. Constitutive activation of protein kinase B and phosphorylation of p47phox by a membrane-targeted phosphoinositide 3-kinase. Curr. Biol. 6: 1271–1278.
- Dulic, V., E. Lees, and S. I. Reed 1992. Association of human cyclin E with a periodic G1-S phase protein kinase. Science 257: 1958–1961.
- Evan, G. I., A. H. Wyllie, C. S. Gilbert, T. D. Littlewood, H. Land, M. Brooks, C. M. Waters, L. Z. Penn, and D. C. Hancock 1992. Induction of apoptosis in fibroblasts by c-myc protein. Cell 69: 119–128.
- Franke, T. F., D. R. Kaplan, and L. C. Cantley 1997. PI3K: downstream AKTion blocks apoptosis. Cell 88: 435–437.
- Franke, T. F., D. R. Kaplan, L. C. Cantley, and A. Toker 1997. Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate. Science 275: 665–668 (Comment.)
- Franke, T. F., S. I. Yang, T. O. Chan, K. Datta, A. Kazlauskas, D. K. Morrison, D. R. Kaplan, and P. N. Tsichlis 1995. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell 81: 727–736.
- Frech, M., M. Andjelkovic, E. Ingley, K. K. Reddy, J. R. Falck, and B. A. Hemmings 1997. High affinity binding of inositol phosphates and phosphoinositides to the pleckstrin homology domain of RAC/protein kinase B and their influence on kinase activity. J. Biol. Chem. 272: 8474–8481.
- Frevert, E. U., and B. B. Kahn 1997. Differential effects of constitutively active phosphatidylinositol 3-kinase on glucose transport, glycogen synthase activity, and DNA synthesis in 3T3-L1 adipocytes. Mol. Cell. Biol. 17: 190–198.
- Gorman, C. 1985. High efficiency gene transfer into mammalian cells, p. 143–190. In: Glover, D. M.. DNA cloning, a practical approach, II: IRL Press, Oxford, United Kingdom.
- Han, J., K. Luby-Phelps, B. Das, X. Shu, Y. Xia, R. D. Mosteller, U. M. Krishna, J. R. Falck, M. A. White, and D. Broek 1998. Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav. Science 279: 558–560.
- Harrington, E. A., M. R. Bennett, A. Fanidi, and G. I. Evan 1994. c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J. 13: 3286–3295.
- Hoang, A. T., K. J. Cohen, J. F. Barrett, D. A. Bergstrom, and C. V. Dang 1994. Participation of cyclin A in Myc-induced apoptosis. Proc. Natl. Acad. Sci. USA 91: 6875–6879.
- Hu, Q., A. Klippel, A. J. Muslin, W. J. Fantl, and L. T. Williams 1995. Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase. Science 268: 100–102.
- Jefferies, H. B., S. Fumagalli, P. B. Dennis, C. Reinhard, R. B. Pearson, and G. Thomas 1997. Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k. EMBO J. 16: 3693–3704.
- Jones, P. F., T. Jakubowicz, F. J. Pitossi, F. Maurer, and B. A. Hemmings 1991. Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily. Proc. Natl. Acad. Sci. USA 88: 4171–4175.
- Kapeller, R., and L. C. Cantley 1994. Phosphatidylinositol 3-kinase. Bioessays 16: 565–576.
- Kauffmann-Zeh, A., P. Rodriguez-Viciana, E. Ulrich, C. Gilbert, P. Coffer, J. Downward, and G. Evan 1997. Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB. Nature 385: 544–548.
- Khwaja, A., P. Rodriguez-Viciana, S. Wennstrom, P. H. Warne, and J. Downward 1997. Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway. EMBO J. 16: 2783–2793.
- Kimura, G., A. Itagaki, and J. Summers 1975. Rat cell line 3y1 and its virogenic polyoma- and sv40-transformed derivatives. Int. J. Cancer 15: 694–706.
- Klippel, A., J. A. Escobedo, M. Hirano, and L. T. Williams 1994. The interaction of small domains between the subunits of phosphatidylinositol 3-kinase determines enzyme activity. Mol. Cell. Biol. 14: 2675–2685.
- Klippel, A., J. A. Escobedo, Q. Hu, and L. T. Williams 1993. A region of the 85-kilodalton (kDa) subunit of phosphatidylinositol 3-kinase binds the 110-kDa catalytic subunit in vivo. Mol. Cell. Biol. 13: 5560–5566.
- Klippel, A., W. M. Kavanaugh, D. Pot, and L. T. Williams 1997. A specific product of phosphatidylinositol 3-kinase directly activates the protein kinase Akt through its pleckstrin homology domain. Mol. Cell. Biol. 17: 338–344.
- Klippel, A., C. Reinhard, W. M. Kavanaugh, G. Apell, M.-A. Escobedo, and L. T. Williams 1996. Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways. Mol. Cell. Biol. 16: 4117–4127.
- Kohn, A. D., F. Takeuchi, and R. A. Roth 1996. Akt, a pleckstrin homology domain containing kinase, is activated primarily by phosphorylation. J. Biol. Chem. 271: 21920–21926.
- Kulik, G., A. Klippel, and M. J. Weber 1997. Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt. Mol. Cell. Biol. 17: 1595–1606.
- Kunz, J., R. Henriquez, U. Schneider, M. Deuter-Reinhard, N. R. Movva, and M. N. Hall 1993. Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 73: 585–596.
- Laemmli, U. K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685.
- Lane, H. A., A. Fernandez, N. J. Lamb, and G. Thomas 1993. p70s6k function is essential for G1 progression. Nature 363: 170–172.
- Li, G., C. D’Souza-Schorey, M. A. Barbieri, R. L. Roberts, A. Klippel, L. T. Williams, and P. D. Stahl 1995. Evidence for phosphatidylinositol 3-kinase as a regulator of endocytosis via activation of Rab5. Proc. Natl. Acad. Sci. USA 92: 10207–10211.
- Littlewood, T. D., D. C. Hancock, P. S. Danielian, M. G. Parker, and G. I. Evan 1995. A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. Nucleic Acids Res. 23: 1686–1690.
- Liu, J. J., J. R. Chao, M. C. Jiang, S. Y. Ng, J. J. Yen, and H. F. Yang-Yen 1995. Ras transformation results in an elevated level of cyclin D1 and acceleration of G1 progression in NIH 3T3 cells. Mol. Cell. Biol. 15: 3654–3663.
- Marte, B. M., and J. Downward 1997. PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem. Sci. 22: 355–358.
- Martin, S. S., T. Haruta, A. J. Morris, A. Klippel, L. T. Williams, and J. M. Olefsky 1996. Activated phosphatidylinositol 3-kinase is sufficient to mediate actin rearrangement and GLUT4 translocation in 3T3-L1 adipocytes. J. Biol. Chem. 271: 17605–17608.
- Martin, S. S., D. W. Rose, A. R. Saltiel, A. Klippel, L. T. Williams, and J. M. Olefsky 1996. Phosphatidylinositol 3-kinase is necessary and sufficient for insulin-stimulated stress fiber breakdown. Endocrinology 137: 5045–5054.
- Matsushime, H., D. E. Quelle, S. A. Shurtleff, M. Shibuya, C. J. Sherr, and J. Y. Kato 1994. D-type cyclin-dependent kinase activity in mammalian cells. Mol. Cell. Biol. 14: 2066–2076.
- Meyerson, M., and E. Harlow 1994. Identification of G1 kinase activity for cdk6, a novel cyclin D partner. Mol. Cell. Biol. 14: 2077–2086.
- Ming, X. F., B. M. Burgering, S. Wennstrom, L. Claesson-Welsh, C. H. Heldin, J. L. Bos, S. C. Kozma, and G. Thomas 1994. Activation of p70/p85 S6 kinase by a pathway independent of p21ras. Nature 371: 426–429 (Comment.)
- Morgan, D. O. 1997. Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu. Rev. Cell Dev. Biol. 13: 261–291.
- Morgan, D. O. 1995. Principles of CDK regulation. Nature 374: 131–134.
- Morgenstern, J. P., and H. Land 1990. Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. Nucleic Acids Res. 18: 3587–3596.
- Nimnual, A. S., B. A. Yatsula, and D. Bar-Sagi 1998. Coupling of Ras and Rac guanosine triphosphatases through the Ras exchanger Sos. Science 279: 560–563.
- Philpott, K. L., M. J. McCarthy, A. Klippel, and L. L. Rubin 1997. Activated phosphatidylinositol 3-kinase and Akt kinase promote survival of superior cervical neurons. J. Cell Biol. 139: 809–815.
- Pullen, N., P. B. Dennis, M. Andjelkovic, A. Dufner, S. C. Kozma, B. A. Hemmings, and G. Thomas 1998. Phosphorylation and activation of p70s6k by PDK1. Science 279: 707–710 (Comment.)
- Reif, K., C. D. Nobes, G. Thomas, A. Hall, and D. A. Cantrell 1996. Phosphatidylinositol 3-kinase signals activate a selective subset of Rac/Rho-dependent effector pathways. Curr. Biol. 6: 1445–1455.
- Reinhard, C., A. Fernandez, N. J. Lamb, and G. Thomas 1994. Nuclear localization of p85s6k: functional requirement for entry into S phase. EMBO J. 13: 1557–1565.
- Roche, S., M. Koegl, and S. A. Courtneidge 1994. The phosphatidylinositol 3-kinase alpha is required for DNA synthesis induced by some, but not all, growth factors. Proc. Natl. Acad. Sci. USA 91: 9185–9189.
- Rodriguez-Viciana, P., P. H. Warne, B. Vanhasenbroeck, M. D. Waterfield, and J. Downward 1996. Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation. EMBO J. 15: 2442–2451.
- Rudolph, B., R. Saffrich, J. Zwicker, B. Henglein, R. Muller, W. Ansorge, and M. Eilers 1996. Activation of cyclin-dependent kinases by Myc mediates induction of cyclin A, but not apoptosis. EMBO J. 15: 3065–3076.
- Sabatini, D. M., H. Erdjument-Bromage, M. Lui, P. Tempst, and S. H. Snyder 1994. RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 78: 35–43.
- Sabers, C. J., M. M. Martin, G. J. Brunn, J. M. Williams, F. J. Dumont, G. Wiederrecht, and R. T. Abraham 1995. Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J. Biol. Chem. 270: 815–822.
- Schultz, A. M., L. E. Henderson, S. Oroszlan, E. A. Garber, and H. Hanafusa 1985. Amino terminal myristoylation of the protein kinase p60src, a retroviral transforming protein. Science 227: 427–429.
- Serunian, L. A., K. R. Auger, and L. C. Cantley 1991. Identification and quantification of polyphosphoinositides produced in response to platelet-derived growth factor stimulation. Methods Enzymol. 198: 78–87.
- Shaw, L. M., I. Rabinovitz, H. H. Wang, A. Toker, and A. M. Mercurio 1997. Activation of phosphoinositide 3-OH kinase by the α6β4 integrin promotes carcinoma invasion. Cell 91: 949–60.
- Sheaff, R. J. 1997. Regulation of mammalian cyclin-dependent kinase 2. Methods Enzymol. 283: 173–193.
- Sherr, C. J. 1996. Cancer cell cycles. Science 274: 1672–1677.
- Sherr, C. J. 1994. G1 phase progression: cycling on cue. Cell 79: 551–555 (Comment.)
- Steiner, P., A. Philipp, J. Lukas, D. Godden-Kent, M. Pagano, S. Mittnacht, J. Bartek, and M. Eilers 1995. Identification of a Myc-dependent step during the formation of active G1 cyclin-cdk complexes. EMBO J. 14: 4814–4826.
- Stephens, L., K. Anderson, D. Stokoe, H. Erdjument-Bromage, G. F. Painter, A. B. Holmes, P. R. Gaffney, C. B. Reese, F. McCormick, P. Tempst, J. Coadwell, and P. T. Hawkins 1998. Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science 279: 710–714 (Comment.)
- Stephens, L. R., T. R. Jackson, and P. T. Hawkins 1993. Agonist-stimulated synthesis of phosphatidylinositol(3,4,5)-trisphosphate: a new intracellular signalling system? Biochim. Biophys. Acta 1179: 27–75.
- Stokoe, D., L. R. Stephens, T. Copeland, P. R. Gaffney, C. B. Reese, G. F. Painter, A. B. Holmes, F. McCormick, and P. T. Hawkins 1997. Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 277: 567–570 (Comment.)
- Takebe, Y., M. Seiki, J.-I. Fujisawa, P. Hoy, K. Yokota, K.-I. Arai, M. Yoshida, and N. Arai 1988. SRα promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol. Cell. Biol. 8: 466–472.
- Tanti, J. F., T. Gremeaux, S. Grillo, V. Calleja, A. Klippel, L. T. Williams, E. Van Obberghen, and Y. Le Marchand-Brustel 1996. Overexpression of a constitutively active form of phosphatidylinositol 3-kinase is sufficient to promote Glut 4 translocation in adipocytes. J. Biol. Chem. 271: 25227–25232.
- Toker, A., and L. C. Cantley 1997. Signalling through the lipid products of phosphoinositide-3-OH kinase. Nature 387: 673–676.
- Traynor-Kaplan, A. E., A. L. Harris, B. L. Thompson, P. Taylor, and L. A. Sklar 1988. An inositol tetrakisphosphate-containing phospholipid in activated neutrophils. Nature 334: 353–356.
- Vlahos, C. J., W. F. Matter, K. Y. Hui, and R. F. Brown 1994. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J. Biol. Chem. 269: 5241–5248.
- Weng, Q. P., K. Andrabi, A. Klippel, M. T. Kozlowski, L. T. Williams, and J. Avruch 1995. Phosphatidylinositol 3-kinase signals activation of p70 S6 kinase in situ through site-specific p70 phosphorylation. Proc. Natl. Acad. Sci. USA 92: 5744–5748.