Comparing the Roles of the p110α and p110β Isoforms of PI3K in Signaling and Cancer

Current Topics in Microbiology and Immunology

Volumn 347, Issue 1, 2010, Pages 55-57

  Ilić, Nina ^a   Roberts, Thomas M ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; CELL SURFACE RECEPTOR; DOXYCYCLINE; ISOENZYME; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PIK3CA P110ALPHA; PIK3CB P110BETA; UNCLASSIFIED DRUG; PROTEIN KINASE B;

ARTICLE; CARCINOGENESIS; CELL GROWTH; CELL MOTILITY; CELL PROLIFERATION; CELL SURVIVAL; ENZYME ACTIVE SITE; ENZYME DEFICIENCY; GENE MUTATION; HUMAN; LUNG ADENOCARCINOMA; NEOPLASM; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; ANIMAL; COMPARATIVE STUDY; DRUG ANTAGONISM; ENZYME ACTIVATION; ENZYMOLOGY; PHYSIOLOGY; REVIEW;

ANIMALS; ENZYME ACTIVATION; HUMANS; ISOENZYMES; NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION;

EID: 79952109738     PISSN: 0070217X     EISSN: None     Source Type: Book Series    
DOI: 10.1007/82-2010-63     Document Type: Article

References (110)

1. al-Aoukaty A, Rolstad B, Maghazachi AA (1999) Recruitment of pleckstrin and phosphoinositide 3-kinase gamma into the cell membranes, and their association with G beta gamma after activation of NK cells with chemokines. J Immunol 162:3249-3255 (Pubitemid 29313571)
2. Alessi DR, James SR, Downes CP, Holmes AB, Gaffney PR, Reese CB, Cohen P (1997) Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr Biol 7:261-269 (Pubitemid 27176852)
3. Arteaga CL (2006) EGF receptor mutations in lung cancer: from humans to mice and maybe back to humans. Cancer Cell 9:421-423 (Pubitemid 43832195)
4. Asano T, Kanda A, Katagiri H, Nawano M, Ogihara T, Inukai K, Anai M, Fukushima Y, Yazaki Y, Kikuchi M, Hooshmand-Rad R, Heldin CH, Oka Y, Funaki M (2000) p110beta is up-regulatedduring differentiation of 3T3-L1 cells and contributes to the highly insulin-responsive glucose transport activity. J Biol Chem 275:17671-17676 (Pubitemid 30430815)
5. Bader AG, Kang S, Vogt PK (2006) Cancer-specific mutations in PIK3CA are oncogenic in vivo. Proc Natl Acad Sci USA 103:1475-1479 (Pubitemid 43191190)
6. Bayascas JR (2008) Dissecting the role of the 3-phosphoinositide- dependent protein kinase-1 (PDK1) signalling pathways. Cell Cycle 7:2978-2982
7. Bellacosa A, Franke TF, Gonzalez-Portal ME, Datta K, Taguchi T, Gardner J, Cheng JQ, Testa JR, Tsichlis PN (1993) Structure, expression and chromosomal mapping of c-akt: relationship to v-akt and its implications. Oncogene 8:745-754 (Pubitemid 23093139)
8. Bi L, Okabe I, Bernard DJ, Wynshaw-Boris A, Nussbaum RL (1999) Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110alpha subunit of phosphoinositide 3-kinase. J Biol Chem 274:10963-10968
9. Bi L, Okabe I, Bernard DJ, Nussbaum RL (2002) Early embryonic lethality in mice deficient in the p110beta catalytic subunit of PI 3-kinase. Mamm Genome 13:169-172 (Pubitemid 34185317)
10. Biggs WH III, Meisenhelder J, Hunter T, Cavenee WK, Arden KC (1999) Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci USA 96:7421-7426 (Pubitemid 29299677)
11. Brachmann SM, Ueki K, Engelman JA, Kahn RC, Cantley LC (2005) Phosphoinositide 3-kinase catalytic subunit deletion and regulatory subunit deletion have opposite effects on insulin sensitivity in mice. Mol Cell Biol 25:1596-1607 (Pubitemid 40282598)
12. Brock C, Schaefer M, Reusch HP, Czupalla C, Michalke M, Spicher K, Schultz G, Nurnberg B (2003) Roles of G beta gamma in membrane recruitment and activation of p110 gamma/p101 phosphoinositide 3-kinase gamma. J Cell Biol 160:89-99 (Pubitemid 36091719)
13. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96:857-868 (Pubitemid 29165088)
14. Brunet A, Datta SR, Greenberg ME (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol 11:297-305 (Pubitemid 32524094)
15. Burnham MR, Harte MT, Bouton AH (1999) The role of SRC-CAS interactions in cellular transformation: ectopic expression of the carboxy terminus of CAS inhibits SRC-CAS interaction but has no effect on cellular transformation. Mol Carcinog 26:20-31 (Pubitemid 29420182)
16. Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296:1655-1657 (Pubitemid 34579158)
17. Chantry D, Vojtek A, Kashishian A, Holtzman DA, Wood C, Gray PW, Cooper JA, Hoekstra MF (1997) p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes. J Biol Chem 272:19236-19241 (Pubitemid 27337713)
18. Chin L, Tam A, Pomerantz J, Wong M, Holash J, Bardeesy N, Shen Q, O'Hagan R, Pantginis J, Zhou H, Horner JW II, Cordon-Cardo C, Yancopoulos GD, DePinho RA (1999) Essential role for oncogenic Ras in tumour maintenance. Nature 400:468-472 (Pubitemid 29361802)
19. Christoforidis S, Miaczynska M, Ashman K, Wilm M, Zhao L, Yip SC, Waterfield MD, Backer JM, Zerial M (1999) Phosphatidylinositol-3-OH kinases are Rab5 effectors. Nat Cell Biol 1:249-252 (Pubitemid 129500945)
20. Ciraolo E, Iezzi M, Marone R, Marengo S, Curcio C, Costa C, Azzolino O, Gonella C, Rubinetto C, Wu H, Dastru W, Martin EL, Silengo L, Altruda F, Turco E, Lanzetti L, Musiani P, Ruckle T, Rommel C, Backer JM, Forni G, Wymann MP, Hirsch E (2008) Phosphoinositide 3-kinase p110beta activity: key role in metabolism and mammary gland cancer but not development. Sci Signal 1:ra3
21. Clement S, Krause U, Desmedt F, Tanti JF, Behrends J, Pesesse X, Sasaki T, Penninger J, Doherty M, Malaisse W, Dumont JE, Le Marchand-Brustel Y, Erneux C, Hue L, Schurmans S (2001) The lipid phosphatase SHIP2 controls insulin sensitivity. Nature 409:92-97 (Pubitemid 32098631)
22. Coffer PJ, Woodgett JR (1991) Molecular cloning and characterisation of a novel putative proteinserine kinase related to the cAMP-dependent and protein kinase C families. Eur J Biochem 201:475-481
23. de Groot RP, Auwerx J, Bourouis M, Sassone-Corsi P (1993) Negative regulation of Jun/AP-1: conserved function of glycogen synthase kinase 3 and the Drosophila kinase shaggy. Oncogene 8:841-847 (Pubitemid 23087414)
24. Denley A, Kang S, Karst U, Vogt PK (2008) Oncogenic signaling of class I PI3K isoforms. Oncogene 27:2561-2574 (Pubitemid 351550883)
25. Deora AA, Win T, Vanhaesebroeck B, Lander HM (1998) A redox-triggered ras-effector interaction. Recruitment of phosphatidylinositol 3'-kinase to Ras by redox stress. J Biol Chem 273:29923-29928 (Pubitemid 28510008)
26. Engelman JA, Luo J, Cantley LC (2006) The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7:606-619 (Pubitemid 44100518)
27. Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, Maira M, McNamara K, Perera SA, Song Y, Chirieac LR, Kaur R, Lightbown A, Simendinger J, Li T, Padera RF, Garcia-Echeverria C, Weissleder R, Mahmood U, Cantley LC, Wong KK (2008) Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 14:1351-1356
28. Fingar DC, Blenis J (2004) Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 23:3151-3171 (Pubitemid 38638827)
29. Foukas LC, Okkenhaug K (2003) Gene-targeting reveals physiological roles and complex regulation of the phosphoinositide 3-kinases. Arch Biochem Biophys 414:13-18 (Pubitemid 36559586)
30. Foukas LC, Claret M, Pearce W, Okkenhaug K, Meek S, Peskett E, Sancho S, Smith AJ, Withers DJ, Vanhaesebroeck B (2006) Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature 441:366-370 (Pubitemid 44050203)
31. Franke TF, Cantley LC (1997) Apoptosis. A Bad kinase makes good. Nature 390:116-117 (Pubitemid 27507959)
32. Fruman DA, Meyers RE, Cantley LC (1998) Phosphoinositide kinases. Annu Rev Biochem 67:481-507 (Pubitemid 28411136)
33. Garami A, Zwartkruis FJ, Nobukuni T, Joaquin M, Roccio M, Stocker H, Kozma SC, Hafen E, Bos JL, Thomas G (2003) Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol Cell 11:1457-1466 (Pubitemid 36776533)
34. Garcia-Echeverria C, Sellers WR (2008) Drug discovery approaches targeting the PI3K/Akt pathway in cancer. Oncogene 27:5511-5526
35. Geering B, Cutillas PR, Nock G, Gharbi SI, Vanhaesebroeck B (2007) Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimers. Proc Natl Acad Sci USA 104:7809-7814 (Pubitemid 47185833)
36. Gentili C, Morelli S, Russo De Boland A (2002) Involvement of PI3-kinase and its association with c-Src in PTH-stimulated rat enterocytes. J Cell Biochem 86:773-783 (Pubitemid 34839978)
37. Gregory MA, Qi Y, Hann SR (2003) Phosphorylation by glycogen synthase kinase-3 controls c-myc proteolysis and subnuclear localization. J Biol Chem 278:51606-51612 (Pubitemid 38020405)
38. Guillermet-Guibert J, Bjorklof K, Salpekar A, Gonella C, Ramadani F, Bilancio A, Meek S, Smith AJ, Okkenhaug K, Vanhaesebroeck B (2008) The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma. Proc Natl Acad Sci USA 105:8292-8297 (Pubitemid 351904749)
39. Gupta S, Ramjaun AR, Haiko P, Wang Y, Warne PH, Nicke B, Nye E, Stamp G, Alitalo K, Downward J (2007) Binding of ras to phosphoinositide 3-kinase p110alpha is required for rasdriven tumorigenesis in mice. Cell 129:957-968 (Pubitemid 46802703)
40. Hanrahan J, Blenis J (2006) Rheb activation of mTOR and S6K1 signaling. Methods Enzymol 407:542-555
41. Harrington LS, Findlay GM, Lamb RF (2005) Restraining PI3K: mTOR signalling goes back to the membrane. Trends Biochem Sci 30:35-42 (Pubitemid 40093739)
42. Hausdorff WP, Pitcher JA, Luttrell DK, Linder ME, Kurose H, Parsons SJ, Caron MG, Lefkowitz RJ (1992) Tyrosine phosphorylation of G protein alpha subunits by pp 60c-src. Proc Natl Acad Sci USA 89:5720-5724
43. Hazeki O, Okada T, Kurosu H, Takasuga S, Suzuki T, Katada T (1998) Activation of PI 3-kinase by G protein betagamma subunits. Life Sci 62:1555-1559 (Pubitemid 28210240)
44. Hooshmand-Rad R, Hajkova L, Klint P, Karlsson R, Vanhaesebroeck B, Claesson-Welsh L, Heldin CH (2000) The PI 3-kinase isoforms p110(alpha) and p110(beta) have differential roles in PDGF-and insulin-mediated signaling. J Cell Sci 113(Pt 2):207-214 (Pubitemid 30088966)
45. Ikenoue T, Kanai F, Hikiba Y, Obata T, Tanaka Y, Imamura J, Ohta M, Jazag A, Guleng B, Tateishi K, Asaoka Y, Matsumura M, Kawabe T, Omata M (2005) Functional analysis of PIK3CA gene mutations in human colorectal cancer. Cancer Res 65:4562-4567 (Pubitemid 40740791)
46. Inoki K, Li Y, Zhu T, Wu J, Guan KL (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 4:648-657 (Pubitemid 34993700)
47. Inoki K, Li Y, Xu T, Guan KL (2003) Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 17:1829-1834 (Pubitemid 36944560)
48. Isakoff SJ, Engelman JA, Irie HY, Luo J, Brachmann SM, Pearline RV, Cantley LC, Brugge JS (2005) Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res 65:10992-11000 (Pubitemid 41713369)
49. Jia S, Liu Z, Zhang S, Liu P, Zhang L, Lee SH, Zhang J, Signoretti S, Loda M, Roberts TM, Zhao JJ (2008) Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature 454:776-779
50. Jones PF, Jakubowicz T, Pitossi FJ, Maurer F, Hemmings BA (1991) Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily. Proc Natl Acad Sci USA 88:4171-4175 (Pubitemid 21914501)
51. Kang S, Bader AG, Vogt PK (2005) Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci USA 102:802-807 (Pubitemid 40282746)
52. Kang S, Denley A, Vanhaesebroeck B, Vogt PK (2006) Oncogenic transformation induced by the p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase. Proc Natl Acad Sci USA 103:1289-1294 (Pubitemid 43191158)
53. Katso R, Okkenhaug K, Ahmadi K, White S, Timms J, Waterfield MD (2001) Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol 17:615-675 (Pubitemid 33096187)
54. Keniry M, Parsons R (2008) The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene 27:5477-5485
55. Knight ZA, Gonzalez B, Feldman ME, Zunder ER, Goldenberg DD,Williams O, Loewith R, Stokoe D, Balla A, Toth B, Balla T, Weiss WA, Williams RL, Shokat KM (2006) A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell 125:733-747
56. Kops GJ, de Ruiter ND, De Vries-Smits AM, Powell DR, Bos JL, Burgering BM (1999) Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature 398:630-634 (Pubitemid 29183692)
57. Krupnick JG, Benovic JL (1998) The role of receptor kinases and arrestins in G protein-coupled receptor regulation. Annu Rev Pharmacol Toxicol 38:289-319 (Pubitemid 28231497)
58. Kurosu H, Maehama T, Okada T, Yamamoto T, Hoshino S, Fukui Y, Ui M, Hazeki O, Katada T (1997) Heterodimeric phosphoinositide 3-kinase consisting of p85 and p110beta is synergistically activated by the betagamma subunits of G proteins and phosphotyrosyl peptide. J Biol Chem 272:24252-24256 (Pubitemid 27418626)
59. Lee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y, Dixon JE, Pandolfi P, Pavletich NP (1999) Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell 99:323-334 (Pubitemid 29519911)
60. Liu J, Liao Z, Camden J, Griffin KD, Garrad RC, Santiago-Perez LI, Gonzalez FA, Seye CI, Weisman GA, Erb L (2004) Src homology 3 binding sites in the P2Y2 nucleotide receptor interact with Src and regulate activities of Src, proline-rich tyrosine kinase 2, and growth factor receptors. J Biol Chem 279:8212-8218 (Pubitemid 38294713)
61. Luttrell LM, Hawes BE, van Biesen T, Luttrell DK, Lansing TJ, Lefkowitz RJ (1996) Role of c-Src tyrosine kinase in G protein-coupled receptor-and Gbetagamma subunit-mediated activation of mitogen-activated protein kinases. J Biol Chem 271:19443-19450 (Pubitemid 26271617)
62. Luttrell LM, Ferguson SS, Daaka Y, Miller WE, Maudsley S, Della Rocca GJ, Lin F, Kawakatsu H, Owada K, Luttrell DK, Caron MG, Lefkowitz RJ (1999) Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science 283:655-661
63. Ma YC, Huang J, Ali S, Lowry W, Huang XY (2000) Src tyrosine kinase is a novel direct effector of G proteins. Cell 102:635-646
64. Maehama T, Dixon JE (1999) PTEN: a tumour suppressor that functions as a phospholipid phosphatase. Trends Cell Biol 9:125-128 (Pubitemid 29161437)
65. Maier U, Babich A, Nurnberg B (1999) Roles of non-catalytic subunits in gbetagamma-induced activation of class I phosphoinositide 3-kinase isoforms beta and gamma. J Biol Chem 274:29311-29317
66. Manning BD (2004) Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. J Cell Biol 167:399-403 (Pubitemid 39489047)
67. Medema RH, Kops GJ, Bos JL, Burgering BM (2000) AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 404:782-787 (Pubitemid 30212408)
68. Moasser MM (2007) The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene 26:6469-6487 (Pubitemid 47530601)
69. Mora A, Komander D, van Aalten DM, Alessi DR (2004) PDK1, the master regulator of AGC kinase signal transduction. Semin Cell Dev Biol 15:161-170 (Pubitemid 38251644)
70. Murga C, Fukuhara S, Gutkind JS (2000) A novel role for phosphatidylinositol 3-kinase beta in signaling from G protein-coupled receptors to Akt. J Biol Chem 275:12069-12073 (Pubitemid 30237781)
71. Naccache PH, Levasseur S, Lachance G, Chakravarti S, Bourgoin SG, McColl SR (2000) Stimulation of human neutrophils by chemotactic factors is associated with the activation of phosphatidylinositol 3-kinase gamma. J Biol Chem 275:23636-23641 (Pubitemid 30624648)
72. Narita Y, Nagane M, Mishima K, Huang HJ, Furnari FB, Cavenee WK (2002) Mutant epidermal growth factor receptor signaling down-regulates p27 through activation of the phosphatidylinositol 3-kinase/Akt pathway in glioblastomas. Cancer Res 62:6764-6769 (Pubitemid 35364149)
73. Nikolakaki E, Coffer PJ, Hemelsoet R, Woodgett JR, Defize LH (1993) Glycogen synthase kinase 3 phosphorylates Jun family members in vitro and negatively regulates their transactivating potential in intact cells. Oncogene 8:833-840 (Pubitemid 23087413)
74. Park CS, Schneider IC, Haugh JM (2003) Kinetic analysis of platelet-derived growth factor receptor/phosphoinositide 3-kinase/Akt signaling in fibroblasts. J Biol Chem 278:37064-37072 (Pubitemid 37175220)
75. Roche S, Koegl M, Courtneidge SA (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
76. Roche S, Downward J, Raynal P, Courtneidge SA (1998) A function for phosphatidylinositol 3-kinase beta (p85alpha-p110beta) in fibroblasts during mitogenesis: requirement for insulinand lysophosphatidic acid-mediated signal transduction. Mol Cell Biol 18:7119-7129 (Pubitemid 28533031)
77. Rodriguez-Fernandez JL, Rozengurt E (1996) Bombesin, bradykinin, vasopressin, and phorbol esters rapidly and transiently activate Src family tyrosine kinases in Swiss 3T3 cells. Dissociation from tyrosine phosphorylation of p125 focal adhesion kinase. J Biol Chem 271:27895-27901 (Pubitemid 26367367)
78. Rossig L, Badorff C, Holzmann Y, Zeiher AM, Dimmeler S (2002) Glycogen synthase kinase-3 couples AKT-dependent signaling to the regulation of p21Cip1 degradation. J Biol Chem 277:9684-9689 (Pubitemid 34968067)
79. Samuels Y, Ericson K (2006) Oncogenic PI3K and its role in cancer. Curr Opin Oncol 18:77-82 (Pubitemid 43740454)
80. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE (2004) High frequency of mutations of the PIK3CA gene in human cancers. Science 304:554 (Pubitemid 38541907)
81. Samuels Y, Diaz LA Jr., Schmidt-Kittler O, Cummins JM, Delong L, Cheong I, Rago C, Huso DL, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE (2005) Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 7:561-573 (Pubitemid 40799249)
82. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005a) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307:1098-1101 (Pubitemid 40262113)
83. Sarbassov DD, Ali SM, Sabatini DM (2005b) Growing roles for the mTOR pathway. Curr Opin Cell Biol 17:596-603 (Pubitemid 41540408)
84. Sauter G, Maeda T, Waldman FM, Davis RL, Feuerstein BG (1996) Patterns of epidermal growth factor receptor amplification in malignant gliomas. Am J Pathol 148:1047-1053 (Pubitemid 26108242)
85. Sears R, Nuckolls F, Haura E, Taya Y, Tamai K, Nevins JR (2000) Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev 14:2501-2514
86. Seoane J, Le HV, Shen L, Anderson SA, Massague J (2004) Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell 117:211-223 (Pubitemid 38496241)
87. Shin HW, Hayashi M, Christoforidis S, Lacas-Gervais S, Hoepfner S, Wenk MR, Modregger J, Uttenweiler-Joseph S, Wilm M, Nystuen A, Frankel WN, Solimena M, De Camilli P, Zerial M (2005) An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway. J Cell Biol 170:607-618 (Pubitemid 41186935)
88. Stephens LR, Eguinoa A, Erdjument-Bromage H, Lui M, Cooke F, Coadwell J, Smrcka AS, Thelen M, Cadwallader K, Tempst P, Hawkins PT (1997) The G beta gamma sensitivity of a PI3K is dependent upon a tightly associated adaptor, p101. Cell 89:105-114 (Pubitemid 27180590)
89. Stoyanov B, Volinia S, Hanck T, Rubio I, Loubtchenkov M, Malek D, Stoyanova S, Vanhaesebroeck B, Dhand R, Nurnberg B et al (1995) Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase. Science 269:690-693
90. Takaishi H, Konishi H, Matsuzaki H, Ono Y, Shirai Y, Saito N, Kitamura T, Ogawa W, Kasuga M, Kikkawa U, Nishizuka Y (1999) Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B. Proc Natl Acad Sci USA 96:11836-11841 (Pubitemid 29502819)
91. Tang ED, Nunez G, Barr FG, Guan KL (1999) Negative regulation of the forkhead transcription factor FKHR by Akt. J Biol Chem 274:16741-16746
92. Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J (2003) Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 13:1259-1268 (Pubitemid 36953298)
93. Terauchi Y, Tsuji Y, Satoh S, Minoura H, Murakami K, Okuno A, Inukai K, Asano T, Kaburagi Y, Ueki K, Nakajima H, Hanafusa T, Matsuzawa Y, Sekihara H, Yin Y, Barrett JC, Oda H, Ishikawa T, Akanuma Y, Komuro I, Suzuki M, Yamamura K, Kodama T, Suzuki H, Yamamura K, Kodama T, Suzuki H, Koyasu S, Aizawa S, Tobe K, Fukui Y, Yazaki Y, Kadowaki T (1999) Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. Nat Genet 21:230-235 (Pubitemid 29070374)
94. Toker A, Newton AC (2000) Cellular signaling: pivoting around PDK-1. Cell 103:185-188
95. Tornillo L, Terracciano LM (2006) An update on molecular genetics of gastrointestinal stromal tumours. J Clin Pathol 59:557-563 (Pubitemid 43886037)
96. Ueki K, Fruman DA, Yballe CM, Fasshauer M, Klein J, Asano T, Cantley LC, Kahn CR (2003) Positive and negative roles of p85 alpha and p85 beta regulatory subunits of phosphoinositide 3-kinase in insulin signaling. J Biol Chem 278:48453-48466 (Pubitemid 37523301)
97. Vanhaesebroeck B, Alessi DR (2000) The PI3K-PDK1 connection: more than just a road to PKB. Biochem J 346(Pt 3):561-576 (Pubitemid 30171014)
98. Vanhaesebroeck B, Waterfield MD (1999) Signaling by distinct classes of phosphoinositide 3-kinases. Exp Cell Res 253:239-254
99. Vanhaesebroeck B, Leevers SJ, Panayotou G, Waterfield MD (1997a) Phosphoinositide 3-kinases: a conserved family of signal transducers. Trends Biochem Sci 22:267-272 (Pubitemid 27310948)
100. Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD (1997b) P110delta, a novel phosphoinositide 3-kinase in leukocytes. Proc Natl Acad Sci USA 94:4330-4335 (Pubitemid 27194241)
101. Vanhaesebroeck B, Leevers SJ, Ahmadi K, Timms J, Katso R, Driscoll PC, Woscholski R, Parker PJ, Waterfield MD (2001) Synthesis and function of 3-phosphorylated inositol lipids. Annu Rev Biochem 70:535-602 (Pubitemid 32662219)
102. Wee S, Wiederschain D, Maira SM, Loo A, Miller C, deBeaumont R, Stegmeier F, Yao YM, Lengauer C (2008) PTEN-deficient cancers depend on PIK3CB. Proc Natl Acad Sci USA 105:13057-13062
103. Wei W, Jin J, Schlisio S, Harper JW, Kaelin WG Jr. (2005) The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer Cell 8:25-33 (Pubitemid 40991812)
104. Yu J, Zhang Y, McIlroy J, Rordorf-Nikolic T, Orr GA, Backer JM (1998) Regulation of the p85/p110 phosphatidylinositol 30-kinase: stabilization and inhibition of the p110alpha catalytic subunit by the p85 regulatory subunit. Mol Cell Biol 18:1379-1387 (Pubitemid 28100902)
105. Yuan TL, Cantley LC (2008) PI3K pathway alterations in cancer: variations on a theme. Oncogene 27:5497-5510
106. Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ (1996) Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell 87:619-628 (Pubitemid 26386936)
107. Zhang Y, Gao X, Saucedo LJ, Ru B, Edgar BA, Pan D (2003) Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat Cell Biol 5:578-581 (Pubitemid 36781094)
108. Zhao L, Vogt PK (2008) Class I PI3K in oncogenic cellular transformation. Oncogene 27:5486-5496
109. Zhao JJ, Liu Z, Wang L, Shin E, Loda MF, Roberts TM (2005) The oncogenic properties of mutant p110alpha and p110beta phosphatidylinositol 3-kinases in human mammary epithelial cells. Proc Natl Acad Sci USA 102:18443-18448 (Pubitemid 43011245)
110. Zhao JJ, Cheng H, Jia S, Wang L, Gjoerup OV, Mikami A, Roberts TM (2006) The p110alpha isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation. Proc Natl Acad Sci USA 103:16296-16300 (Pubitemid 44715190)