Inhibition of protein kinase B/Akt: Implications for cancer therapy

Pharmacology and Therapeutics

Volumn 93, Issue 2-3, 2002, Pages 243-251

  Hill, Michelle M ^a   Hemmings, Brian A ^a  

^a FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH   (Switzerland)

Author keywords

Akt; Apoptosis; Cancer; Cell cycle; Diabetes; PKB

Indexed keywords

ANTINEOPLASTIC AGENT; CARBOXYL TERMINAL MODULATOR PROTEIN; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN KINASE B; PROTEIN KINASE B INHIBITOR; UNCLASSIFIED DRUG; AKT1 PROTEIN, HUMAN; ENZYME INHIBITOR; IMATINIB; ONCOPROTEIN; PROTEIN SERINE THREONINE KINASE; PYRIMIDINE DERIVATIVE; STAUROSPORINE;

APOPTOSIS; CANCER CHEMOTHERAPY; CONFERENCE PAPER; DRUG EFFICACY; DRUG MECHANISM; ENZYME ACTIVITY; ENZYME INHIBITION; GENE MUTATION; MAMMAL CELL; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; VIRUS CELL TRANSFORMATION; DIABETES MELLITUS; DRUG ANTAGONISM; DRUG EFFECT; ENZYMOLOGY; FEMALE; HUMAN; MALE; METABOLISM; NEOPLASM; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

APOPTOSIS; DIABETES MELLITUS; ENZYME INHIBITORS; FEMALE; HUMAN; MALE; NEOPLASMS; PROTO-ONCOGENE PROTEINS; PYRIMIDINES; SIGNAL TRANSDUCTION; STAUROSPORINE; STRUCTURE-ACTIVITY RELATIONSHIP; SUPPORT, NON-U.S. GOV'T; HUMANS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-AKT;

EID: 0035990924     PISSN: 01637258     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0163-7258(02)00193-6     Document Type: Conference Paper

References (97)

1. Discovery of PDK1, one of the missing links in insulin signal transduction
2. Mechanism of activation of protein kinase B by insulin and IGF-1
3. Molecular basis for the substrate specificity of protein kinase B; Comparison with MAPKAP kinase-1 and p70 S6 kinase
4. 3-Phosphoinositide-dependent protein kinase-1 (PDK1): Structural and functional homology with the Drosophilia DSTPK61 kinase
5. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα
6. Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B
7. Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors
8. Role of translocation in the activation and function of protein kinase B
9. A 3-phosphoinositide-dependent protein kinase-1 (PDK1) docking site is required for the phosphorylation of protein kinase Cζ (PKCζ) and PKC-related kinase 2 by PDK1
10. Control of apoptosis by Rel/NF-κB transcription factors
11. Treatment of human glioblastoma cells with the staurosporine derivative CGP 41251 inhibits CDC2 and CDK2 kinase activity and increases radiation sensitivity
12. Growth inhibition induced by Ro 31-8220 and calphostin C in human glioblastoma cell lines is associated with apoptosis and inhibition of CDC2 kinase
13. A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region
14. Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas
15. Identification of a pocket in the PDK1 kinase domain that interacts with PIF and the C-terminal residues of PKA
16. The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB
17. Oncogenic kinase signalling
18. Ten years of protein kinase B signalling: A hard Akt to follow
19. A human protein kinase Bγ with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain
20. Two splice variants of protein kinase Bγ have different regulatory capacity depending on the presence or absence of the regulatory phosphorylation site serine 472 in the carboxyl-terminal hydrophobic domain
21. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor
22. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction
23. Regulation of cell death protease caspase-9 by phosphorylation
24. Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: Identification of five sites of phosphorylation in vivo
25. A role for protein phosphatase 2A-like activity, but not atypical protein kinase Cζ in the inhibition of protein kinase B/Akt and glycogen by palmitate
26. Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene
27. AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas
28. Amplication of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA
29. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKBβ)
30. Akt1/PKBα is required for normal growth but dispensable for maintenance of glucose homeostasis in mice
31. Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP-dependent and protein kinase C families
32. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
33. Role of phosphatidylinositol 3,4,5-trisphosphate in regulating the activity and localization of 3-phosphoinositide-dependent protein kinase-1
34. Akt phosphorylation of BAD couple survival signals to the cell-intrinsic death machinery
35. Cellular survival: A play in three Akts
36. Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase
37. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt
38. Ca2+-independent smooth muscle contraction. A novel function for intergrin-linked kinase
39. Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization
40. CREB is a regulatory target for the protein kinase Akt/PKB
41. Proliferation, cell cycle and apoptosis in cancer
42. PKC412 - A protein kinase inhibitor with a broad therapeutic potential
43. Effect of phosphoinositide-dependent kinase 1 on protein kinase B translocation and its subsequent activation
44. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase
45. High affinity binding of inositol phosphates and phosphoinositides to the pleckstrin homology domain of RAC/protein kinase B and their influence on kinase activity
46. A phosphoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1
47. Akt phosphorylation site found in human caspase-9 is absent in mouse caspase-9
48. Identification of flow-dependent endothelial nitric-oxide synthase phosphorylation sites by mass spectrometry and regulation of phosphorylation and nitric oxide production by the phosphatidylinositol 3-kinase inhibitor LY294002
49. Peroxovanadate induces tyrosine phosphorylation of phosphoinositide-dependent protein kinase-1: Potential involvement of src kinase
50. Protein kinase B (PKB/Akt) - A key regulator of glucose transport?
51. Regulation of cell adhesion and anchorage-dependent growth by a new β1-intergrin-linked protein kinase
52. Insulin-stimulated protein kinase B phosphorylation on Ser-473 is independent of its activity and occurs through a staurosporine-insensitive kinase
53. Induction of apoptosis by ASK1, a mammalian MAPKKK that activities SAPK/JNK and p38 signaling pathways
54. Molecular cloning of a second form of rac protein kinase
55. Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily
56. Induction of NF-κB by the Akt/PKB kinase
57. Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1
58. Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation
59. Direct control of the Forkhead transcription factor AFX by protein kinase B
60. C-Myb transcription is activated by protein kinase B (PKB) following interleukin 2 stimulation of T cells and is required for PKB-mediated protection from apoptosis
61. Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis
62. Signal-dependent membrane targeting by pleckstrin homology (PH) domains
63. Integrin-linked kinase regulates phosphorylation of serine 473 of protein kinase B by an indirect mechanism
64. Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane
65. STI571: Targeting BCR-ABL as therapy for CML
66. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus
67. kip 1
68. Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bβ
69. Inactivation and dephosphorylation of protein kinase Bα(PKBα) promoted by hyperosmotic stress
70. Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines
71. Peptide and protein library screening defines optimal substrate motifs for AKT/PKB
72. NF-κB activation by tumour necrosis factor requires the Akt serine-threonine kinase
73. Akt1 induces extracellular matrix invasion and matrix metalloproteinase-2 activity in mouse mammary epithelial cells
74. Identification of tyrosine phosphorylation sites on 3-phosphoinositide-dependent protein kinase-1 and their role in regulating kinase activity
75. Inhibition of integrin-linked kinase (ILK) suppresses activation of protein kinase B/Akt and induces cell cycle arrest and apoptosis of PTEN-mutant prostate cancer cells
76. Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: Critical roles for kinase activity and amino acids arginine 211 and serine 343
77. Oxidative stress and vanadate induce tyrosine phosphorylation of phosphoinositide-dependent kinase 1 (PDK1)
78. Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein
79. Inhibition of cAMP-response element-binding protein activity decreases protein kinase B/Akt expression in 3T3-L1 adipocytes and induces apoptosis
80. Modulation of Akt kinase activity by binding to Hsp90
81. Mammary gland involution is delayed by activated Akt in transgenic mice
82. 7-Hydroxystaurosporine (UCN-01) induces apoptosis in human colon carcinoma and leukemia cells independently of p53
83. Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2; Amplification of AKT1 in a primary human gastric adenocarcinoma
84. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
85. Staurosporine and conventional anticancer drugs induce overlapping, yet distinct pathways of apoptosis and caspase activation
86. Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-triphosphate-dependent activation of protein kinase B
87. Dual role of phosphatidylinositol-3,4,5-triphosphate in the activation of protein kinase B
88. Inhibition of integrin linked kinase (ILK) suppresses β-catenin-Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail, in APC-/- human colon carcinoma cells
89. The antiapoptotic gene mcl-1 is up-regulated by the phosphadylinositol 3-kinase/Akt signaling pathway through a transcription factor complex containing CREB
90. The role of 3-phosphoinositide-dependent protein kinase 1 in activating AGC kinases defined in embryonic stem cells
91. Tumor suppressor PTEN: Modulator of cell signaling, growth, migration and apoptosis
92. Integrin-linked kinase (ILK): A "hot" therapeutic target
93. Drosophila integrin-linked kinase is required at sites of integrin adhesion to link the cytoskeleton to the plasma membrane
94. Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells
95. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation
96. Akt regulates cell survival and apoptosis at a postmitochondrial level
97. Raf-MEK-Erk cascade in anoikis is controlled by Rac1 and Cdc42 via Akt