Phosphoinositide 3-kinase inhibition in cancer treatment

Expert Opinion on Investigational Drugs

Volumn 10, Issue 6, 2001, Pages 1085-1098

  Berrie, C P ^a  

^a Ist Ricerche Farmacol Mario Negri ^*  (Italy)

Author keywords

Apoptosis; Cancer; Cell growth; Cell migration; Cell proliferation; Cytoskeleton; Membrane trafficking; Phosphoinositide 3 kinase

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; ATM PROTEIN; B LYMPHOCYTE RECEPTOR; CASEIN KINASE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DNA; DNA DEPENDENT PROTEIN KINASE; EPIDERMAL GROWTH FACTOR; G PROTEIN COUPLED RECEPTOR; IMMUNOSUPPRESSIVE AGENT; INSULIN; INSULIN RECEPTOR SUBSTRATE 1; MYOSIN LIGHT CHAIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PHOSPHATIDYLINOSITOL 3,4 BISPHOSPHATE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE; PLATELET DERIVED GROWTH FACTOR; PLECKSTRIN; PROTEIN P50; PROTEIN P55; PROTEIN P85; RAPAMYCIN; T LYMPHOCYTE RECEPTOR; UNINDEXED DRUG; WORTMANNIN;

ANIMAL CELL; BINDING SITE; CANCER; CANCER CELL; CANCER CONTROL; CANCER GROWTH; CANCER INVASION; CANCER THERAPY; CELL DIFFERENTIATION; CELL GROWTH; CELL MOTILITY; CELL PROLIFERATION; CELL SURVIVAL; CORRELATION FUNCTION; DEPHOSPHORYLATION; DNA REPAIR; DRUG EFFICACY; DRUG SPECIFICITY; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; IN VIVO STUDY; ISOMER; MEMBRANE TRANSPORT; METASTASIS; MOLECULAR RECOGNITION; MOUSE; NONHUMAN; PROTEIN TARGETING; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANDROSTADIENES; ANIMALS; CHROMONES; ENZYME INHIBITORS; HUMANS; MORPHOLINES; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 0034982825     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.10.6.1085     Document Type: Review

References (120)

1. Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase
2. Identification and characterization of a new oncogene derived from the regulatory subunit of phosphoinositide 3-kinase
3. PIK3CA is implicated as an oncogene in ovarian cancer
4. Activation of phosphatidylinositol 3-kinase is sufficient for cell cycle entry and promotes cellular changes characteristic of oncogenic transformation
5. Phosphatidylinositol 3-kinases in tumor progression
6. Inhibitors of phosphatidylinositol signalling as antiproliferative agents
7. Therapeutic intervention and signaling
8. PI-3 kinase in signal transduction, cell transformation, and as a target for chemoprevention of cancer
9. Lipids on the move: Phosphoinositide 3-kinases in leukocyte function
10. Patterns within protein/polyphosphoinositide interactions provide specific targets for therapeutic intervention
11. PI3-kinase inhibition: A target for drug development?
12. 2 enzymes: Regulation and inhibition
13. 2
14. Inositol-lipid-specific phospholipase C isoenzymes and their differential regulation by receptors
15. Phospholipase D and cell signaling
16. 2 hydrolysis and regulation of phospholipase C isozymes
17. Agonist-stimulated synthesis of phosphatidylinositol (3,4,5)-trisphosphate: A new intracellular signalling system?
18. The synthesis and cellular roles of phosphatidylinositol 4,5-bisphosphate
19. Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol 3-phosphate
20. PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells
21. Oncogenes and signal transduction
22. Phosphoinositide 3-kinase: A new effector in signal transduction?
23. Pleckstrin homology domains
24. Pleckstrin homology domains: A common fold with diverse functions
25. The function of inositol high polyphosphate binding proteins
26. Phosphoinositide lipids as signalling molecules: Common themes for signal transduction, cytoskeletal regulation, and membrane trafficking
27. Large and diverse numbers of human diseases with HIKE mutations
28. The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity
29. FYVE-finger proteins - Effectors of an inositol lipid
30. Phosphoinositide binding domains: Embracing 3-phosphate
31. Cellular functions of phosphatidylinositol 3-phosphate and FYVE domain proteins
32. The emerging field of receptor-mediated inhibitory signalling: SHP or SHIP?
33. Inositol lipid 5-phosphatases - Traffic signals and signal traffic
34. SHIPs ahoy
35. The tumour suppressor PTEN/MMAC1 dephosphorylates the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate
36. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway
37. PTEN/MMAC1/TEP1 in signal transduction and tumorigenesis
38. Phosphoinositide 3-kinases: A conserved family of signal transducers
39. Structure and function of phosphoinositide 3-kinases
40. Signalling by distinct classes of phosphoinositide 3-kinases
41. The Gβγ sensitivity of a PI3K is dependent upon a tightly-associated adaptor, p101
42. PI 3-kinase is a dual specificity enzyme: Autoregulation by an intrinsic protein-serine kinase activity
43. Autophosphorylation of p110δ phosphoinositide 3-kinase: A new paradigm for the regulation of lipid kinases in vitro and in vivo
44. SHP-1 regulates Lck-induced phosphatidylinositol 3-kinase phosphorylation and activity
45. Human phosphoinositide 3-kinase C2β, the role of calcium and the C2 domain in enzyme activity
46. Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors
47. The Class II phosphoinositide 3-kinase PI3K-C2α is concentrated in the trans-Golgi network and present in clathrin-coated vesicles
48. Presence and activation of nuclear phosphoinositide 3-kinase C2β during the compensatory liver growth
49. Phosphoinositide 3-kinases and their FYVE-domain-containing effectors as regulators of vascuolar/lysosomal membrane trafficking pathways
50. The role of phosphoinositide 3-kinase lipid products in cell function
51. Signaling through phosphoinositide 3-kinases: The lipids take centre stage
52. Leukocytes navigate by compass: Roles of PI3Kγ and its lipid products
53. Phosphoinositides in membrane traffic
54. Phosphoinositide signaling and the regulation of membrane trafficking in yeast
55. PDK1 - A kinase at the hub of things
56. Cellular survival: A play in three Akts
57. The PI3K-PDK1 connection: More than just a road to PKB
58. Cytohesins and centaurins: Mediators of PI 3-kinase-regulated Arf signaling
59. Wortmannin, a potent and selective inhibitor of phosphatidylinositol 3-kinase
60. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002)
61. Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction
62. Cloning and characterisation of a wortmannin-sensitive human phosphatidylinositol 4-kinase
63. 2 activity in Swiss 3T3 cells
64. Specificity and mechanism of action of some commonly used protein kinase inhibitors
65. Cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin
66. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine
67. Moving in mysterious ways
68. Regulation of chemotaxis by the platelet-derived growth factor receptor-β
69. Activation of phosphoinositide 3-kinase is required for PDGF-stimulated membrane ruffling
70. Membrane ruffling and chemotaxis transduced by the PDGF β-receptor require the binding site for phosphatidylinositol 3′-kinase
71. Xid-like immunodeficiency in mice with disruption of the p85α subunit of phosphoinositide 3-kinase
72. Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85α
73. Increased insulin sensitivity and hypoglycaemia in mice lacking the p85α subunit of phosphoinositide 3-kinase
74. Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85α
75. p85α gene generates three isoforms of regulatory subunit for phosphatidylinositol 3-kinase (PI 3-kinase), p50α, p55α, and p85α, with different PI 3-kinase activity elevating responses to insulin
76. Five isoforms of the phosphatidylinositol 3-kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations
77. The PI 3-kinase isoforms p110α and p110β have different roles in PDGF- and insulin-mediated signaling
78. When is a lipid kinase not a lipid kinase? When it is a protein kinase
79. Bifurcation of lipid and protein kinase signals of PI3Kγ to the protein kinases PKB and MAPK
80. Crystal structure of the tyrosine phosphatase SHP-2
81. Identification of two SH3-binding motifs in the regulatory subunit of phosphatidylinositol 3-kinase
82. Identification of amino acid residues required for a specific interaction between Src-tyrosine kinase and proline-rich region of phosphatidylinositol 3′-kinase
83. Negative regulation of PI 3-kinase by Ruk, a novel adaptor protein
84. A novel integrin-activated pathway forms PKB/Akt-stimulatory phosphatidylinositol 3,4-bisphosphate via phosphatidylinositol 3-phosphate in platelets
85. Biphasic activation of PKBα/Akt in platelets
86. Distinct phosphatidylinositol 3-kinase lipid products accumulate upon oxidative and osmotic stress and lead to different cellular responses
87. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast and prostate cancer
88. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers
89. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta
90. The PTEN tumor suppressor protein: An antagonist of phosphoinositide 3-kinase signaling
91. PTEN: Life as a tumor suppressor
92. Inositol 3,4,5,6-tetrakisphosphate inhibits the calmodulin-dependent protein kinase II-activated chloride conductance in T84 colonic epithelial cells
93. Inositol 1,3,4-trisphoaphate acts in vivo as a specific regulator of cellular signaling by inositol 3,4,5,6-tetrakisphosphate
94. D-myo-inositol 1,4,5,6-tetrakisphosphate produced in human intestinal epithelial cells in response to Salmonella invasion inhibits phosphoinositide 3-kinase signaling pathways
95. Novel functional PI 3-kinase antagonists inhibit cell growth and tumorigenicity in human cancer cell lines
96. Occurrence and extracellular actions of inositol pentakis-and hexakisphosphate in mammalian brain
97. Binding of inositol phosphate to DNA-PK and stimulation of double-strand break repair
98. Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae
99. Ceramide in the eukaryotic stress response
100. Cross-talk between phosphatidylinositol 3-kinase and sphingomyelinase pathways as a mechanism for cell survival/death decisions
101. Ceramide dissociates 3′-phosphoinositide production from pleckstrin homology domain translocation
102. Signal-dependent membrane targeting by pleckstrin homology (PH) domains
103. The pleckstrin homology domains of dynamin isoforms require oligomerization for high affinity phosphoinositide binding
104. Identification and analysis of PH-domain-containing targets of phosphatidylinositol 3-kinase using a novel in vivo assay in yeast
105. Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities
106. The PH superfold: A structural scaffold for multiple functions
107. Targeting of Tiam1 to the plasma membrane requires the cooperative function of the N-terminal pleckstrin homology domain and an adjacent protein interaction domain
108. The solution structure and dynamics of the pleckstrin homology domain of G-protein-coupled receptor kinase 2 (β-adrenergic receptor kinase 1). A binding partner of Gβγ subunits
109. Activation of phospholipase Cγ by PI-3-kinase-induced PH-domain-mediated membrane targeting
110. Activation of phospholipase C-gamma by phosphatidylinositol 3,4,5-trisphosphate
111. 2+ oscillations in cardiac cells
112. Discovering novel chemotherapeutic drugs for the third millennium
113. Problems in the development of target-based drugs
114. The use of single-nucleotide polymorphism maps in pharmacogenomics
115. Drug firms to create public database of genetic mutations
116. The catalytic subunit of phosphoinositide 3-kinase: Requirements for oncogenicity
117. Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells
118. A phosphatidylinositol 3,4,5-trisphosphate analogue with low serum-protein-binding affinity
119. Intracellular delivery of phosphoinositides and inositol phosphates using polyamine carriers
120. Small GTP-binding proteins