The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB

Experimental Cell Research

Volumn 253, Issue 1, 1999, Pages 210-229

  Kandel, Eugene S ^a   Hay, Nissim ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GROWTH FACTOR RECEPTOR; INSULIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN SERINE THREONINE KINASE;

AMINO ACID SEQUENCE; APOPTOSIS; CANCER INHIBITION; CARCINOGENESIS; CELL CYCLE; CELL SURVIVAL; ENZYME ACTIVITY; ENZYME INDUCTION; ENZYME REGULATION; GLUCOSE TRANSPORT; PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN SYNTHESIS; REVIEW; SECOND MESSENGER; TRANSCRIPTION REGULATION;

EID: 0033604585     PISSN: 00144827     EISSN: None     Source Type: Journal    
DOI: 10.1006/excr.1999.4690     Document Type: Article

References (190)

1. Staal S. P., Hartley J. W., Rowe W. P. Isolation of transforming murine leukemia viruses from mice with a high incidence of spontaneous lymphoma. Proc. Natl. Acad. Sci. USA. 74:1977;3065-3067.
2. Bellacosa A., Testa J. R., Staal S. P., Tsichlis P. N. A retroviral oncogene, akt, encoding a serine/threonine kinase containing an SH2-like region. Science. 254:1991;274-277.
3. Coffer P. J., Woodgett J. R. Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP-dependent and protein kinase C families. Eur. J. Biochem. 201:1991;475-481.
4. Jones P. F., Jakubowicz T., Pitossi F. J., Maurer F., Hemmings B. A. Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily. Proc. Natl. Acad. Sci. USA. 88:1991;4171-4175.
5. Chen P., Lee K. S., Levin D. E. A pair of putative protein kinase genes (YPK1 and YPK2) is required for cell growth in Saccharomyces cerevisiae. Mol. Gen. Genet. 236:1993;443-447.
6. Franke T. F., Tartof K. D., Tsichlis P. N. The SH2-like Akt homology (AH) domain of c-akt is present in multiple copies of the genome of vertebrate and invertebrate eucaryotes: Cloning and characterization of the Drosophila melanogaster c-akt homolog Dakt1. Oncogene. 9:1994;141-148.
7. Andjelkovic M., Jones P. F., Grossniklaus U., Cron P., Schier A. F., Dick M., Bilbe G., Hemmings B. A. Developmental regulation of expression and activity of multiple forms of the Drosophila RAC protein kinase. J. Biol. Chem. 270:1995;4066-4075.
8. Chang H. W., Aoki M., Fruman D., Auger K. R., Bellacosa A., Tsichlis P. N., Cantley L. C., Roberts T. M., Vogt P. K. Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase. Science. 276:1997;1848-1850.
9. Paradis S., Ruvkun G. Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev. 12:1998;2488-2498.
10. Meili R., Ellsworth C., Lee S., Reddy T. B., Ma H., Firtel R. A. Chemoattractant-mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium. EMBO J. 18:1999;2092-2105.
11. Tanaka K., Adachi H., Konishi H., Iwamatsu A., Ohkawa K., Shirai T., Nagata S., Kikkawa U., Fukui Y. Identification of protein kinase B (PKB) as a phosphatidylinositol 3,4,5-trisphosphate binding protein in Dictyostelium discoideum. Biosci. Biotechnol. Biochem. 63:1999;368-372.
12. Burgering B. M., Coffer P. J. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature. 376:1995;599-602.
13. Franke T. F., Yang S., Chan T. O., Datta K., Kazlauskas A., Morrison D. K., Kaplan D. R., Tsichlis P. N. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell. 81:1995;727-736.
14. Cross D. A., Aless D. R., Cohen P., Andjelkovich M., Hemmings B. A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 378:1995;785-789.
15. Dudek H., Datta S. R., Franke T. F., Birnbaum M. J., Yao R., Cooper G. M., Segal R. A., Kaplan D. R., Greenberg M. E. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science. 275:1997;661-665.
16. Kauffmann-Zeh A., Rodriguez-Viciana P., Ulrich E., Gilbert C., Coffer P., Downward J., Evan G. Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB. Nature. 385:1997;544-548.
17. Kennedy S. G., Wagner A. J., Conzen S. D., Jordan J., Bellacosa A., Tsichlis P. N., Hay N. The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev. 11:1997;701-713.
18. Kulik G., Klippel A., Weber M. J. Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt. Mol. Cell. Biol. 17:1997;1595-1606.
19. Jones P. F., Jakubowicz T., Hemmings B. A. Molecular cloning of a second form of rac protein kinase. Cell Regul. 2:1991;1001-1009.
20. Altomare D. A., Guo K., Cheng J. Q., Sonoda G., Walsh K., Testa J. R. Cloning, chromosomal localization and expression analysis of the mouse Akt2 oncogene. Oncogene. 11:1995;1055-1060.
21. Brodbeck D., Cron P., Hemmings B. A. A human protein kinase Bgamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain. J. Biol. Chem. 274:1999;9133-9136.
22. Nakatani K., Sakaue H., Thompson D. A., Weigel R. J., Roth R. A. Identification of a human Akt3 (protein kinase B γ) which contains the regulatory serine phosphorylation site. Biochem. Biophys. Res. Commun. 257:1999;906-910.
23. Konishi H., Matsuzaki H., Tanaka M., Ono Y., Tokunaga C., Kuroda S., Kikkawa U. Activation of RAC-protein kinase by heat shock and hyperosmolarity stress through a pathway independent of phosphatidylinositol 3-kinase. Proc. Natl. Acad. Sci. USA. 93:1996;7639-7643.
24. Webster M. K., Goya L., Ge Y., Maiyar A. C., Firestone G. L. Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum. Mol. Cell. Biol. 13:1993;2031-2040.
25. Kobayashi T., Cohen P. Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2. Biochem. J. 339:1999;319-328.
26. Casamayor A., Torrance P. D., Kobayashi T., Thorner J., DR A. Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast. Curr. Biol. 9:1999;186-197.
27. Bellacosa A., Franke T. F., Portal E. G., Datta K., Taguchi T., Gardner J., Cheng J. Q., Testa J. R., Tsichlis P. N. Structure, expression and chromosomal mapping of c-akt: Relationship to v-akt and its implications. Oncogene. 8:1993;745-754.
28. Altomare D. A., Lyons G. E., Mitsuuchi Y., Cheng J. Q., Testa J. R. Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin. Oncogene. 116:1998;2407-2411.
29. Owada Y., Utsunomiya A., Yoshimoto T., Kondo H. Expression of mRNA for Akt, serine-threonine protein kinase, in the brain during development and its transient enhancement following axotomy of hypoglossal nerve. J. Mol. Neurosci. 9:1997;27-33.
30. Walker K. S., Deak M., Paterson A., Hudson K., Cohen P., Alessi D. R. Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: Comparison with protein kinase B alpha. Biochem. J. 331:1998;299-308.
31. Fujio Y., Guo K., Mano T., Mitsuuchi Y., Testa J. R., Walsh K. Cell cycle withdrawal promotes myogenic induction of Akt, a positive modulator of myocyte survival. Mol. Cell. Biol. 19:1999;5073-5082.
32. Ahmed N. N., Franke T. F., Bellacosa A., Datta K., Portal M. E. G., Taguchi T., Testa J. R., P. N. T. The proteins encoded by c-akt and v-akt differ in posttranslational modification, subcellular localization and oncogenic potential. Oncogene. 8:1993;1957-1963.
33. Andjelkovic M., Alessi D. R., Meier R., Fernandez A., Lamb N. J., Frech M., Cron P., Cohen P., Lucocq J. M., Hemmings B. A. Role of translocation in the activation and function of protein kinase B. J. Biol. Chem. 272:1997;31515-31524.
34. Kohn A. D., Kovacina K. S., Roth R. A. Insulin stimulates the kinase activity of Rac-PK, a pleckstrin homology domain containing Ser/Thr kinase. EMBO J. 14:1995;4288-4295.
35. Klippel A., Reinhard C., Kavanaugh W. M., Apell G., Escobedo M. A., Williams L. T. Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways. Mol. Cell. Biol. 16:1996;4117-4127.
36. Bellacosa A., Chan T. O., Ahmed N. N., Datta K., Malstrom S., Stokoe D., McCormick F., Feng J., Tsichlis P. Akt activation by growth factors is a multiple-step process: The role of the PH domain. Oncogene. 17:1998;313-325.
37. James S. R., Downes C. P., Gigg R., Grove S. J., Holmes A. B., Alessi D. R. Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation. Biochem. J. 315:1996;709-713.
38. Franke T. F., Kaplan D. R., Cantley L. C., Toker A. T. Direct regulation of the akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate. Science. 275:1997;665-667.
39. Klippel A., Kavanaugh W. M., Pot D., Williams L. A specific product of phosphatidylinositol 3-kinase directly activates the protein kinase Akt through its pleckstrin homology domain. Mol. Cell. Biol. 17:1997;338-344.
40. Stokoe D., Stephens L. R., Copeland T., Gaffney P. R. J., Reese C. B., Painter G. F., Holmes A. B., McCormick F., Hawkins P. T. Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science. 277:1997;567-570.
41. Stephens L., Anderson K., Stokoe D., Erdjument-Bromage H., Painter G. F., Holmes A. B., Gaffney P. R., Reese C. B., McCormick F., Tempst P., Coadwell J., Hawkins P. T. Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science. 279:1998;710-714.
42. Aman M. J., Lamkin T. D., Okada H., Kurosaki T., Ravichandran K. S. The inositol phosphatase SHIP inhibits Akt/PKB activation in B cells. J. Biol. Chem. 273:1998;33922-33928.
43. Liu Q., Sasaki T., Kozieradzki I., Wakeham A., Itie A., Dumont D. J., Penninger J. M. SHIP is a negative regulator of growth factor receptor-mediated PKB/Akt activation and myeloid cell survival. Genes Dev. 13:1999;786-791.
44. Datta K., Franke T. F., Chan T. O., Makris A., Yang S., Kaplan D. R., Morrison D. K., Golemis E. A., Tsichlis P. N. AH/PH domain/mediated interaction between Akt molecules and its potential role in Akt regulation. Mol. Cell. Biol. 15:1995;2304-2310.
45. Coffer P. J., Jin J., Woodgett J. R. Protein kinase B (c-Akt): A multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem. J. 335:1998;1-13.
46. Khwaja A., Rodriguez-Viciana P., Wenstrom S., Warne P. H., Downward J. Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway. EMBO J. 16:1997;2783-2793.
47. King W. G., Mattaliano M. D., Chan T. O., Tsichlis P. N., Brugge J. S. Phosphatidylinositol 3-kinase is required for integrin-stimulated AKT and Raf-1/mitogen-activated protein kinase pathway activation. Mol. Cell. Biol. 17:1997;4406-4418.
48. Banfic H., Tang X., Batty I. H., Downes C. P., Chen C., Rittenhouse S. E. A novel integrin-activated pathway forms PKB/Akt-stimulatory phosphatidylinositol 3,4-bisphosphate via phosphatidylinositol 3-phosphate in platelets. J. Biol. Chem. 273:1998;13-16.
49. Parry R. V., Reif K., Smith G., Sansom D. M., Hemmings B. A., Ward S. G. Ligation of the T cell co-stimulatory receptor CD28 activates the serine-threonine protein kinase protein kinase B. Eur. J. Immunol. 27:1997;2495-24501.
50. Tilton B., Andjelkovic M., Didichenko S. A., Hemmings B. A., Thelen M. G-protein-coupled receptors and Fcgamma-receptors mediate activation of Akt/protein kinase B in human phagocytes. J. Biol. Chem. 272:1997;28096-28101.
51. Gringhuis S. I., de Leij L. F., Coffer P. J., Vellenga E. Signaling through CD5 activates a pathway involving phosphatidylinositol 3-kinase, Vav, and Rac1 in human mature T lymphocytes. Mol. Cell. Biol. 18:1998;1725-1735.
52. Murga C., Laguinge L., Wetzker R., Cuadrado A., Gutkind J. S. Activation of Akt/protein kinase B by G protein-coupled receptors. A role for alpha and beta gamma subunits of heterotrimeric G proteins acting through phosphatidylinositol-3-OH kinasegamma. J. Biol. Chem. 273:1998;19080-19085.
53. Polakiewicz R. D., Schieferl S. M., Gingras A. C., Sonenberg N., Comb M. J. mu-Opioid receptor activates signaling pathways implicated in cell survival and translational control. J. Biol. Chem. 273:1998;23534-23541.
54. Gold M. R., Scheid M. P., Santos L., Dang-Lawson M., Roth R. A., Matsuuchi L., Duronio V., Krebs D. L. The B cell antigen receptor activates the akt (protein kinase B)/glycogen synthase kinase-3 signaling pathway via phosphatidylinositol 3-kinase. J. Immunol. 163:1999;1894-1905.
55. Takahashi T., Taniguchi T., Konishi H., Kikkawa U., Ishikawa Y., Yokoyama M. Activation of Akt/protein kinase B after stimulation with angiotensin II in vascular smooth muscle cells. Am. J. Physiol. 276:1999;H1927-1934.
56. Ushio-Fukai M., Alexander R. W., Akers M., Yin Q., Fujio Y., Walsh K., Griendling K. K. Reactive oxygen species mediate the activation of Akt/protein kinase B by angiotensin II in vascular smooth muscle cells. J. Biol. Chem. 274:1999;22699-22704.
57. Yang H., Raizada M. K. Role of phosphatidylinositol 3-kinase in angiotensin II regulation of norepinephrine neuromodulation in brain neurons of the spontaneously hypertensive rat. J. Neurosci. 19:1999;2413-2423.
58. Borgatti P., Zauli G., Colamussi M. L., Gibellini D., Previati M., Cantley L. L., Capitani S. Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells. Eur. J. Immunol. 27:1997;2805-2811.
59. Meili R., Cron P., Hemmings B. A., Ballmer-Hofer K. Protein kinase B/Akt is activated by polyomavirus middle-T antigen via a phosphatidylinositol 3-kinase-dependent mechanism. Oncogene. 16:1998;903-907.
60. Downward J. Role of phosphoinositide-3-OH kinase in Ras signaling. Adv. Second Messenger Phosphoprotein Res. 31:1997;1-10.
61. Marte B. M., Rodriguez-Viciana P., Wennstrom S., Warne P. H., Downward J. R-Ras can activate the phosphoinositide 3-kinase but not the MAP kinase arm of the Ras effector pathways. Curr. Biol. 7:1997;63-70.
62. Alessi D. R., Caudwell F. B., Andjelkovic M., Hemmings B. A., Cohen P. Molecular basis for the substrate specificity of protein kinase B: Comparison with MAPKAP kinase-1 and p70 S6 kinase. Fed. Eur. Biochem. Soc. 399:1996;333-338.
63. Alessi D., James S., Downes C. P., Holmes A., Gaffney P., Reese C., Cohen P. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα Curr. Biol. 7:1997;261-269.
64. Alessi D. R., Deak M., Casamayor A., Caudwell F. B., Morrice N., Norman D. G., Gaffney P., Reese C. B., MacDougall C. N., Harbison D., Ashworth A., Bownes M. 3-Phosphoinositide-dependent protein kinase-1 (PDK1): Structural and functional homology with the Drosophila DSTPK61 kinase. Curr. Biol. 7:1997;776-789.
65. Currie R. A., Walker K. S., Gray A., Deak M., Casamayor A., Downes C. P., Cohen P., Alessi D. R., Lucocq J. Role of phosphatidylinositol 3,4,5-trisphosphate in regulating the activity and localization of 3-phosphoinositide-dependent protein kinase-1. Biochem. J. 337:1999;575-583.
66. Anderson K. E., Coadwell J., Stephens L. R., Hawkins P. T. Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B. Curr. Biol. 8:1998;684-691.
67. Paradis S., Ailion M., Toker A., Thomas J. H., Ruvkun G. A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev. 13:1999;1438-1452.
68. Delcommenne M., Tan C., Gray V., Rue L., Woodgett J., Dedhar S. Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc. Natl. Acad. Sci. USA. 95:1998;11211-11216.
69. Balendran A., Casamayor A., Deak M., Paterson A., Gaffney P., Currie R., Downes C. P., Alessi D. R. PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2. Curr. Biol. 9:1999;393-404.
70. Andjelkovic M., Jakubowicz T., Cron P., Ming X. F., Han J. W., Hemmings B. A. Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors. Proc. Natl. Acad. Sci. USA. 93:1996;5699-5704.
71. Meier R., Alessi D. R., Cron P., Andjelkovic M., Hemmings B. A. Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase B beta. J. Biol. Chem. 272:1997;30491-30497.
72. Meier R., Thelen M., Hemmings B. A. Inactivation and dephosphorylation of protein kinase Balpha (PKBalpha) promoted by hyperosmotic stress. EMBO J. 17:1998;7294-7303.
73. Li H. L., Davis W. W., Whiteman E. L., Birnbaum M. J., Pure E. The tyrosine kinases Syk and Lyn exert opposing effects on the activation of protein kinase Akt/PKB in B lymphocytes. Proc. Natl. Acad. Sci. USA. 96:1999;6890-6895.
74. Cantley L. C., Neel B. G. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc. Natl. Acad. Sci. USA. 96:1999;4240-4245.
75. Li D. M., Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res. 57:1997;2124-2129.
76. Myers M. P., Stolarov J. P., Eng C., Li J., Wang S. I., Wigler M. H., Parsons R., Tonks N. K. P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc. Natl. Acad. Sci. USA. 94:1997;9052-9057.
77. Maehama T., Dixon J. E. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J. Biol. Chem. 273:1998;13375-13378.
78. Myers M. P., Pass I., Batty I. H., Van der Kaay J., Stolarov J. P., Hemmings B. A., Wigler M. H., Downes C. P., Tonks N. K. The lipid phosphatase activity of PTEN is critical for its tumor suppressor function. Proc. Natl. Acad. Sci. USA. 95:1998;13513-13518.
79. Haas-Kogan D., Shalev N., Wong M., Mills G., Yount G., Stokoe D. Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC. Curr. Biol. 8:1998;1195-1198.
80. Stambolic V., Suzuki A., de la Pompa J. L., Brothers G. M., Mirtsos C., Sasaki T., Ruland J., Penninger J. M., Siderovski D. P., Mak T. W. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell. 95:1998;29-39.
81. Li D. M., Sun H. PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell cycle arrest in human glioblastoma cells. Proc. Natl. Acad. Sci. USA. 95:1998;15406-15411.
82. Wu X., Senechal K., Neshat M. S., Whang Y. E., Sawyers C. L. The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway. Proc. Natl. Acad. Sci. USA. 95:1998;15587-15591.
83. Ogg S., Ruvkun G. The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway. Mol. Cell. 2:1998;887-893.
84. Habib T., Hejna J. A., Moses R. E., Decker S. J. Growth factors and insulin stimulate tyrosine phosphorylation of the 51C/SHIP2 protein. J. Biol. Chem. 273:1998;18605-18609.
85. Ishihara H., Sasaoka T., Hori H., Wada T., Hirai H., Haruta T., Langlois W. J., Kobayashi M. Molecular cloning of rat SH2-containing inositol phosphatase 2 (SHIP2) and its role in the regulation of insulin signaling. Biochem. Biophys. Res. Commun. 260:1999;265-272.
86. Liu A. X., Testa J. R., Hamilton T. C., Jove R., Nicosia S. V., Cheng J. Q. AKT2, a member of the protein kinase B family, is activated by growth factors, v-Ha-ras, and v-src through phosphatidylinositol 3-kinase in human ovarian epithelial cancer cells. Cancer Res. 58:1998;2973-2977.
87. Mitsuuchi Y., Johnson S. W., Moonblatt S., Testa J. R. Translocation and activation of AKT2 in response to stimulation by insulin. J. Cell. Biochem. 70:1998;433-441.
88. Sable C. L., Filippa N., Hemmings B., Van Obberghen E. cAMP stimulates protein kinase B in a Wortmannin-insensitive manner. FEBS Lett. 409:1997;253-257.
89. Filippa N., Sable C. L., Filloux C., Hemmings B., Van Obberghen E. Mechanism of protein kinase B activation by cyclic AMP-dependent protein kinase. Mol. Cell. Biol. 19:1999;4989-5000.
90. Yano S., Tokumitsu H., Soderling T. R. Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway. Nature. 396:1998;584-587.
91. Konishi H., Matsuzaki H., Tanaka M., Takemura Y., Kuroda S., Ono Y., Kikkawa U. Activation of protein kinase B (Akt/RAC-protein kinase) by cellular stress and its association with heat shock protein Hsp27. FEBS Lett. 410:1997;493-498.
92. Moule S. K., Welsh G. I., Edgell N. J., Foulstone E. J., Proud C. G., Denton R. M. Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal fat cells. Activation of protein kinase B by wortmannin-sensitive and -insensitive mechanisms. J. Biol. Chem. 272:1997;7713-7719.
93. Carmeliet P., Lampugnani M. G., Moons L., Breviario F., Compernolle V., Bono F., Balconi G., Spagnuolo R., Oostuyse B., Dewerchin M., Zanetti A., Angellilo A., Mattot V., Nuyens D., Lutgens E., Clotman F., de Ruiter M. C., Gittenberger-de Groot A., Poelmann R., Lupu F., Herbert J. M., Collen D., Dejana E. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell. 98:1999;147-157.
94. Deprez J., Vertommen D., Alessi D. R., Hue L., Rider M. H. Phosphorylation and activation of heart 6-phosphofucto-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades. J. Biol. Chem. 272:1997;17269-17275.
95. Kitamura T., Kitamura Y., Kuroda S., Hino Y., Ando M., Kotani K., Konishi H., Matsuzaki H., Kikkawa U., Ogawa W., Kasuga M. Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt. Mol. Cell. Biol. 19:1999;6286-6296.
96. Sonenberg N., Gingras A. C. The mRNA 5′ cap-binding protein eIF4E and control of cell growth. Curr. Opin. Cell Biol. 10:1998;268-275.
97. Gingras A. C., Kennedy S. G., O'Leary M. A., Sonenberg N., Hay N. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev. 12:1998;502-513.
98. Brunn G. J., Hudson C. C., Sekulic A., Williams J. M., Hosoi H., Houghton P. J., Lawrence J. Jr., Abraham R. T. Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science. 277:1997;99-101.
99. Scott P. H., Brunn G. J., Kohn A. D., Roth R. A., Lawrence J. C. J. Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway. Proc. Natl. Acad. Sci. USA. 95:1998;7772-7777.
100. Gingras A. C., Gygi S. P., Raught B., Polakiewicz R. D., Abraham R. T., Hoekstra M. F., Aebersold R., Sonenberg N. Regulation of 4E-BP1 phosphorylation: A novel two-step mechanism. Genes Dev. 13:1999;1422-1437.
101. Ballou L. M., Luther H., Thomas G. MAP2 kinase and 70K S6 kinase lie on distinct signalling pathways. Nature. 349:1991;348-350.
102. Dufner A., Andjelkovic M., Burgering B. M., Hemmings B. A., Thomas G. Protein kinase B localization and activation differentially affect S6 kinase 1 activity and eukaryotic translation initiation factor 4E-binding protein 1 phosphorylation. Mol. Cell. Biol. 19:1999;4525-4534.
103. Wang X., Campbell L. E., Miller C. M., Proud C. G. Amino acid availability regulates p70 S6 kinase and multiple translation factors. Biochem. J. 334:1998;261-267.
104. Davis R. J., Bennicelli J. L., Macina R. A., Nycum L. M., Biegel J. A., Barr F. G. Structural characterization of the FKHR gene and its rearrangement in alveolar rhabdomyosarcoma. Hum. Mol. Genet. 4:1995;2355-2362.
105. Borkhardt A., Repp R., Haas O. A., Leis T., Harbott J., Kreuder J., Hammermann J., Henn T., Lampert F. Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23). Oncogene. 14:1997;195-202.
106. Hillion J., Le Coniat M., Jonveaux P., Berger R., Bernard O. A. AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily. Blood. 90:1997;3714-3719.
107. Anderson M. J., Viars C. S., Czekay S., Cavenee W. K., Arden K. C. Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily. Genomics. 47:1998;187-199.
108. Biggs W., Meisenhelder J., Hunter T., Cavenee W. K., Arden K. C. Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc. Natl. Acad. Sci. USA. 96:1999;7421-7426.
109. Brunet A., Bonni A., Zigmond M. J., Lin M. Z., Juo P., Hu L. S., Anderson M. J., Arden K. C., Blenis J., Greenberg M. E. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 96:1999;857-868.
110. Kops G. J., de Ruiter N. D., De Vries-Smits A. M., Powell D. R., Bos J. L., Burgering B. M. Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature. 398:1999;630-634.
111. Rena G., Guo S., Cichy S. C., Unterman T. G., Cohen P. Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J. Biol. Chem. 274:1999;17179-17183.
112. Guo S., Rena G., Cichy S., He X., Cohen P., Unterman T. Phosphorylation of serine 256 by protein kinase B disrupts transactivation by FKHR and mediates effects of insulin on insulin-like growth factor-binding protein-1 promoter activity through a conserved insulin response sequence. J. Biol. Chem. 274:1999;17184-17192.
113. Datta S. R., Dudek H., Tao X., Masters S., Fu H., Gotoh Y., Greenberg M. E. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 91:1997;231-241.
114. del Peso L., Gonzalez-Garcia M., Page C., Herrera R., Nunez G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science. 278:1997;687-689.
115. Cardone M. H., Roy N., Stennicke H. R., Salvesen G. S., Franke T. F., Stanbridge E., Frisch S., Reed J. C. Regulation of cell death protease caspase-9 by phosphorylation. Science. 282:1998;1318-1321.
116. Dimmeler S., Fleming I., Fisslthaler B., Hermann C., Busse R., Zeiher A. M. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 399:1999;601-605.
117. Fulton D., Gratton J. P., McCabe T. J., Fontana J., Fujio Y., Walsh K., Franke T. F., Papapetropoulos A., Sessa W. C. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. 399:1999;597-601.
118. Wang J. M., Chao J. R., Chen W., Kuo M. L., Yen J. J., Yang-Yen H. F. The antiapoptotic gene mcl-1 is up-regulated by the phosphatidylinositol 3-kinase/Akt signaling pathway through a transcription factor complex containing CREB. Mol. Cell. Biol. 19:1999;6195-6206.
119. Brennan P., Babbage J. W., Burgering B. M., Groner B., Reif K., Cantrell D. A. Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F. Immunity. 7:1997;679-689.
120. Kane L. P., Shapiro V. S., Stokoe D., Weiss A. Induction of NF-kappaB by the Akt/PKB kinase. Curr. Biol. 9:1999;601-604.
121. Miller J. R., Moon R. T. Signal transduction through beta-catenin and specification of cell fate during embryogenesis. Genes Dev. 10:1996;2527-2539.
122. de Groot R. P., Auwerx J., Bourouis M., Sassone-Corsi P. Negative regulation of Jun/AP-1: Conserved function of glycogen synthase kinase 3 and the Drosophila kinase shaggy. Oncogene. 8:1993;841-847.
123. Nikolakaki E., Coffer P. J., Hemelsoet R., Woodgett J. R., Defize L. H. Glycogen synthase kinase 3 phosphorylates Jun family members in vitro and negatively regulates their transactivating potential in intact cells. Oncogene. 8:1993;833-840.
124. Wang D., Sul H. S. Insulin stimulation of the fatty acid synthase promoter is mediated by the phosphatidylinositol 3-kinase pathway. Involvement of protein kinase B/Akt. J. Biol. Chem. 273:1998;25420-25426.
125. Wang Y., Falasca M., Schlessinger J., Malstrom S., Tsichlis P., Settleman J., Hu W., Lim B., Prywes R. Activation of the c-fos serum response element by phosphatidyl inositol 3-kinase and rho pathways in HeLa cells. Cell Growth Differ. 9:1998;513-522.
126. Hajduch E., Alessi D. R., Hemmings B. A., Hundal H. S. Constitutive activation of protein kinase B alpha by membrane targeting promotes glucose and system A amino acid transport, protein synthesis, and inactivation of glycogen synthase kinase 3 in L6 muscle cells. Diabetes. 47:1998;1006-1013.
127. Barthel A., Okino S. T., Liao J., Nakatani K., Li J., Whitlock J. Jr., Roth R. A. Regulation of GLUT1 gene transcription by the serine/threonine kinase Akt1. J. Biol. Chem. 274:1999;20281-20286.
128. Agati J. M., Yeagley D., Quinn P. G. Assessment of the roles of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, protein kinase B, and protein kinase C in insulin inhibition of cAMP-induced phosphoenolpyruvate carboxykinase gene transcription. J. Biol. Chem. 273:1998;18751-18759.
129. Mazure N. M., Chen E. Y., Laderoute K. R., Giaccia A. J. Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible factor-1 transcriptional element. Blood. 90:1997;3322-3331.
130. Redpath N. T., Foulstone E. J., Proud C. G. Regulation of translation elongation factor-2 by insulin via a rapamycin-sensitive signalling pathway. EMBO J. 15:1996;2291-2297.
131. Jefferies H. B., Fumagalli S., Dennis P. B., Reinhard C., Pearson R. B., Thomas G. Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k. EMBO J. 16:1997;3693-3704.
132. Welsh G. I., Miller C. M., Loughlin A. J., Price N. T., Proud C. G. Regulation of eukaryotic initiation factor eIF2B: Glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin. FEBS Lett. 421:1998;125-130.
133. Kohn A. D., Summers S. A., Birnbaum M. J., Roth R. A. Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. J. Biol. Chem. 271:1996;31372-31378.
134. Cong L. N., Chen H., Li Y., Zhou L., McGibbon M. A., Taylor S. I., Quon M. J. Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells. Mol. Endocrinol. 11:1997;1881-1890.
135. Tanti J. F., Grillo S., Gremeaux T., Coffer P. J., Van Obberghen E., Le Marchand-Brustel Y. Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes. Endocrinology. 138:1997;2005-2010.
136. Barbieri M. A., Hoffenberg S., Roberts R., Mukhopadhyay A., Pomrehn A., Dickey B. F., Stahl P. D. Evidence for a symmetrical requirement for Rab5-GTP in in vitro endosome-endosome fusion. J. Biol. Chem. 273:1998;25850-25855.
137. Muise-Helmericks R. C., Grimes H. L., Bellacosa A., Malstrom S. E., Tsichlis P. N., Rosen N. Cyclin D expression is controlled post-transcriptionally via a phosphatidylinositol 3-kinase/Akt-dependent pathway. J. Biol. Chem. 273:1998;29864-29872.
138. Diehl J. A., Cheng M., Roussel M. F., Sherr C. J. Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 12:1998;3499-3511.
139. Ahmed N. N., Grimes H. L., Bellacosa A., Chan T. O., Tsichlis P. N. Transduction of interleukin-2 antiapoptotic and proliferative signal via Akt protein kinase. Proc. Natl. Acad. Sci. USA. 94:1997;3627-3632.
140. Sun H., Lesche R., Li D. M., Liliental J., Zhang H., Gao J., Gavrilova N., Mueller B., Liu X., Wu H. PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Proc. Natl. Acad. Sci. USA. 96:1999;6199-6204.
141. Yao R., Cooper G. M. Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by the nerve growth factor. Science. 267:1995;2003-2005.
142. S6K activity. Oncogene. 13:1996;343-351.
143. Parry R. V., Reif K., Smith G., Sansom D. M., Hemmings B. A., Ward S. G. Ligation of the T cell co-stimulatory receptor CD28 activates the serine-threonine protein kinase protein kinase B. Eur. J. Immunol. 27:1997;2495-2501.
144. Songyang Z., Baltimore D., Cantley L. C., Kaplan D. R., Fanke T. F. Interleukin 3-dependent survival by the Akt protein kinase. Proc. Natl. Acad. Sci. USA. 94:1997;11345-11350.
145. Blume-Jensen P., Janknecht R., Hunter T. The kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of Bad on Ser136. Curr. Biol. 8:1998;779-782.
146. Kelley T. W., Graham M. M., Doseff A. I., Pomerantz R. W., Lau S. M., Ostrowski M. C., Franke T. F., Marsh C. B. Macrophage colony-stimulating factor promotes cell survival through Akt/protein kinase B. J. Biol. Chem. 274:1999;26393-26398.
147. Leverrier Y., Thomas J., Mathieu A. L., Low W., Blanquier B., Marvel J. Role of PI3-kinase in Bcl-X induction and apoptosis inhibition mediated by IL-3 or IGF-1 in Baf-3 cells. Cell Death Differ. 6:1999;290-296.
148. Crowder R. J., Freeman R. S. The survival of sympathetic neurons promoted by potassium depolarization, but not by cyclic AMP, requires phosphatidylinositol 3-kinase and Akt. J. Neurochem. 73:1999;466-475.
149. Dolcet X., Egea J., Soler R. M., Martin-Zanca D., Comella J. X. Activation of phosphatidylinositol 3-kinase, but not extracellular-regulated kinases, is necessary to mediate brain-derived neurotrophic factor-induced motoneuron survival. J. Neurochem. 73:1999;521-531.
150. Eves E. M., Xiong W., Bellacosa A., Kennedy S. G., Tsichlis P. N., Rosner M. R., Hay N. Akt, a target of phosphatidylinositol 3-kinase, inhibits apoptosis
151. Gerber H. P., McMurtrey A., Kowalski J., Yan M., Keyt B. A., Dixit V., Ferrara N. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J. Biol. Chem. 273:1998;30336-30343.
152. Kontos C. D., Stauffer T. P., Yang W. P., York J. D., Huang L., Blanar M. A., Meyer T., Peters K. G. Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt. Mol. Cell. Biol. 18:1998;4131-4140.
153. Gautreau A., Poullet P., Louvard D., Arpin M. Ezrin, a plasma membrane-microfilament linker, signals cell survival through the phosphatidylinositol 3-kinase/Akt pathway. Proc. Natl. Acad. Sci. USA. 96:1999;7300-7305.
154. Gibson S., Tu S., Oyer R., Anderson S. M., Johnson G. L. Epidermal growth factor protects epithelial cells against Fas-induced apoptosis. Requirement for Akt activation. J. Biol. Chem. 274:1999;17612-17618.
155. Kennedy S. G., Kandel E. S., Cross T. K., Hay N. Akt/protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Mol. Cell. Biol. 19:1999;5800-5810.
156. Parry R., Smith G., Reif K., Sansom D. M., Ward S. Activation of the PI3K effector protein kinase B following ligation of CD28 or Fas. Biochem. Soc. Trans. 25:1997;S589.
157. Chen R. H., Su Y. H., Chuang R. L., Chang T. Y. Suppression of transforming growth factor-beta-induced apoptosis through a phosphatidylinositol 3-kinase/Akt-dependent pathway. Oncogene. 17:1998;1959-1968.
158. Chen R. H., Chang M. C., Su Y. H., Tsai Y. T., Kuo M. L. Interleukin-6 inhibits transforming growth factor-beta-induced apoptosis through the phosphatidylinositol 3-kinase/Akt and signal transducers and activators of transcription 3 pathways. J. Biol. Chem. 274:1999;23013-23019.
159. Staveley B. E., Ruel L., Jin J., Stambolic V., Mastronardi F. G., Heitzler P., Woodgett J. R., Manoukian A. S. Genetic analysis of protein kinase B (AKT) in Drosophila. Curr. Biol. 8:1998;599-602.
160. Bergmann A., Agapite J., McCall K., Steller H. The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling. Cell. 95:1998;331-341.
161. Green D., Reed J. Mitochondria and apoptosis. Science. 281:1998;1309-1312.
162. Thornberry N. A., Lazebnik Y. Caspases: Enemies within. Science. 281:1998;312-316.
163. Adams J. M., Cory S. The Bcl-2 protein family: Arbiters of cell survival. Science. 281:1998;1322-1326.
164. L and Bcl-2, displaces Bax and promotes cell death. Cell. 80:1995;285-291.
165. Varkey J., Chen P., Jemmerson R., Abrams J. M. Altered cytochrome c display precedes apoptotic cell death in Drosophila. J. Cell Biol. 144:1999;701-710.
166. Pap M., Cooper G. M. Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-kinase/Akt cell survival pathway. J. Biol. Chem. 273:1998;19929-19932.
167. Vander Heiden M. G., Chandel N. S., Schumacker P. T., Thompson C. B. Bcl-xL prevents cell death following growth factor withdrawal by facilitating mitochondrial ATP/ADP exchange. Mol. Cell. 3:1999;159-167.
168. Cheng J. Q., Altomare D. A., Klein M. A., Lee W. C., Kruh G. D., Lissy N. A., Testa J. R. Transforming activity and mitosis-related expression of the AKT2 oncogene: Evidence suggesting a link between cell cycle regulation and oncogenesis. Oncogene. 14:1997;2793-2801.
169. Aoki M., Batista O., Bellacosa A., Tsichlis P., Vogt P. K. The akt kinase: Molecular determinants of oncogenicity. Proc. Natl. Acad. Sci. USA. 95:1998;14950-14955.
170. Di Cristofano A., Pesce B., Cordon-Cardo C., Pandolfi P. P. Pten is essential for embryonic development and tumour suppression. Nat. Genet. 19:1998;348-355.
171. Suzuki A., de la Pompa J. L., Stambolic V., Elia A. J., Sasaki T., del Barco Barrantes I., Ho A., Wakeham A., Itie A., Khoo W., Fukumoto M., Mak T. W. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr. Biol. 8:1998;1169-1178.
172. Podsypanina K., Ellenson L. H., Nemes A., Gu J., Tamura M., Yamada K. M., Cordon-Cardo C., Catoretti G., Fisher P. E., Parsons R. Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc. Natl. Acad. Sci. USA. 96:1999;1563-1568.
173. Shayesteh L., Lu Y., Kuo W. L., Baldocchi R., Godfrey T., Collins C., Pinkel D., Powell B., Mills G. B., Gray J. W. PIK3CA is implicated as an oncogene in ovarian cancer [see comments]. Nat. Genet. 21:1999;99-102.
174. Staal S. P. Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: Amplification of AKT1 in a primary human gastric adenocarcinoma. Proc. Natl. Acad. Sci. USA. 84:1987;5034-5037.
175. Bellacosa A., Feo D. D., Godwin A. K., Bell D. W., Cheng J. Q., Altomare D. A., Wan M., Dubeau L., Scambia G., Masciullo V., Ferrandina G., Panici P. B., Mancuso S., Neri G., Testa J. R. Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int. J. Cancer. 64:1995;280-285.
176. Cheng J. Q., Ruggeri B., Klein W. M., Sonoda G., Altomare D. A., Watson D. K., Testa J. R. Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc. Natl. Acad. Sci. USA. 93:1996;3636-3641.
177. Miwa W., Yasuda J., Murakami Y., Yashima K., Sugano K., Sekine T., Kono A., Egawa S., Yamaguchi K., Hayashizaki Y., Sekiya T. Isolation of DNA sequences amplified at chromosome 19q13.1-q13.2 including the AKT2 locus in human pancreatic cancer. Biochem. Biophys. Res. Commun. 225:1996;968-974.
178. Thompson F. H., Nelson M. A., Trent J. M., Guan X. Y., Liu Y., Yang J. M., Emerson J., Adair L., Wymer J., Balfour C., Massey K., Weinstein R., Alberts D. S., Taetle R. Amplification of 19q13.1-q13.2 sequences in ovarian cancer. G-band, FISH, and molecular studies. Cancer Genet. Cytogenet. 87:1996;55-62.
179. Ruggeri B. A., Huang L., Wood M., Cheng J. Q., Testa J. R. Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. Mol. Carcinog. 21:1998;81-86.
180. Nakatani K., Thompson D. A., Barthel A., Sakaue H., Liu W., Weigel R. J., Roth R. A. Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines. J. Biol. Chem. 274:1999;21528-21532.
181. Skorski T., Wlodarski P., Daheron L., Salomoni P., Nieborowska-Skorska M., Majewski M., Wasik M., Calabretta B. BCR/ABL-mediated leukemogenesis requires the activity of the small GTP-binding protein Rac. Proc. Natl. Acad. Sci. USA. 95:1998;11858-11862.
182. Li J., Simpson L., Takahashi M., Miliaresis C., Myers M. P., Tonks N., Parsons R. The PTEN/MMAC1 tumor suppressor induces cell death that is rescued by the AKT/protein kinase B oncogene. Cancer Res. 58:1998;5667-5672.
183. Krook A., Roth R. A., Jiang X. J., Zierath J. R., Wallberg-Henriksson H. Insulin-stimulated Akt kinase activity is reduced in skeletal muscle from NIDDM subjects. Diabetes. 47:1998;1281-1286.
184. Rondinone C. M., Carvalho E., Wesslau C., Smith U. P. Impaired glucose transport and protein kinase B activation by insulin, but not okadaic acid, in adipocytes from subjects with Type II diabetes mellitus. Diabetologia. 42:1999;819-825.
185. Eldar-Finkelman H., Schreyer S. A., Shinohara M. M., LeBoeuf R. C., Krebs E. G. Increased glycogen synthase kinase-3 activity in diabetes- and obesity-prone C57BL/6J mice. Diabetes. 48:1999;1662-1666.
186. Hansen L., Fjordvang H., Rasmussen S. K., Vestergaard H., Echwald S. M., Hansen T., Alessi D., Shenolikar S., Saltiel A. R., Barbetti F., Pedersen O. Mutational analysis of the coding regions of the genes encoding protein kinase B-alpha and -beta, phosphoinositide-dependent protein kinase-1, phosphatase targeting to glycogen, protein phosphatase inhibitor-1, and glycogenin: Lessons from a search for genetic variability of the insulin-stimulated glycogen synthesis pathway of skeletal muscle in NIDDM patients. Diabetes. 48:1999;403-407.
187. Gagnon A., Chen C. S., Sorisky A. Activation of protein kinase B and induction of adipogenesis by insulin in 3T3-L1 preadipocytes: Contribution of phosphoinositide-3,4,5-trisphosphate versus phosphoinositide-3,4-bisphosphate. Diabetes. 48:1999;691-698.
188. Jiang B. H., Aoki M., Zheng J. Z., Li J., Vogt P. K. Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase Akt/protein kinase B. Proc. Natl. Acad. Sci. USA. 96:1999;2077-2081.
189. Du K., Montminy M. CREB is a regulatory target for the protein kinase Akt/PKB. J. Biol. Chem. 273:1998;32377-32379.
190. Auruch J., Zhang X. F., Kyriakis J. M. Raf meets Ras: Completing the framework of a signal transduction pathway. Trends Biochem. Sci. 19:1994;279-283.