Disruption of PH-kinase domain interactions leads to oncogenic activation of AKT in human cancers

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 47, 2012, Pages 19368-19373

  Parikh, Chaitali ^a   Janakiraman, Vasantharajan ^a   Wu, Wen I ^b   Foo, Catherine K ^a   Kljavin, Noelyn M ^a   Chaudhuri, Subhra ^a   Stawiski, Eric ^a   Lee, Brian ^a   Lin, Jie ^a   Li, Hong ^a   Lorenzo, Maria N ^a   Yuan, Wenlin ^a   Guillory, Joseph ^a   Jackson, Marlena ^a   Rondon, Jesus ^a   Franke, Yvonne ^a   Bowman, Krista K ^a   Sagolla, Meredith ^a   Stinson, Jeremy ^a   Wu, Thomas D ^a   Wu, Jiansheng ^a   Stokoe, David ^a   Stern, Howard M ^a   Brandhuber, Barbara J ^b   Lin, Kui ^a   Skelton, Nicholas J ^a   Seshagiri, Somasekar ^a   more..

^a GENENTECH INC   (United States)

^b ARRAY BIOPHARMA INC   (United States)

Author keywords

AKT targeting; BaF3; Interdomain; Next generation sequencing; PI3K pathway

Indexed keywords

PROTEIN KINASE B;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARCINOGENESIS; CARCINOGENICITY; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; ENZYME ACTIVATION; HUMAN; HUMAN TISSUE; MOUSE; NEOPLASM; NONHUMAN; PLECKSTRIN HOMOLOGY KINASE DOMAIN INTERACTION; PRIORITY JOURNAL; PROTEIN DOMAIN; SIGNAL TRANSDUCTION; SOMATIC MUTATION;

ALLOSTERIC REGULATION; ANIMALS; CELL LINE, TUMOR; CELL MEMBRANE; CELL TRANSFORMATION, NEOPLASTIC; ENZYME ACTIVATION; HUMANS; MICE; MODELS, MOLECULAR; MUTANT PROTEINS; MUTATION; NEOPLASMS; NIH 3T3 CELLS; ONCOGENES; PROTEIN BINDING; PROTEIN KINASE INHIBITORS; PROTEIN TRANSPORT; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION;

MURINAE;

EID: 84869774399     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1204384109     Document Type: Article

References (48)

1. Vasudevan KM, Garraway LA (2010) AKT signaling in physiology and disease. Curr Top Microbiol Immunol 347:105-133.
2. Brazil DP, Hemmings BA (2001) Ten years of protein kinase B signalling: A hard Akt to follow. Trends Biochem Sci 26(11):657-664.
3. Hanada M, Feng J, Hemmings BA (2004) Structure, regulation and function of PKB/AKT - a major therapeutic target. Biochim Biophys Acta 1697(1-2):3-16.
4. Fayard E, Xue G, Parcellier A, Bozulic L, Hemmings BA (2010) Protein kinase B (PKB/Akt), a key mediator of the PI3K signaling pathway. Curr Top Microbiol Immunol 346:31-56.
5. Bellacosa A, et al. (1998) Akt activation by growth factors is a multiple-step process: The role of the PH domain. Oncogene 17(3):313-325.
6. Scheid MP, Woodgett JR (2003) Unravelling the activation mechanisms of protein kinase B/Akt. FEBS Lett 546(1):108-112.
7. Nicholson KM, Anderson NG (2002) The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 14(5):381-395.
8. Sansal I, Sellers WR (2004) The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol 22(14):2954-2963.
9. Chalhoub N, Baker SJ (2009) PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol 4:127-150.
10. Carpten JD, et al. (2007) A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 448(7152):439-444.
11. Landgraf KE, Pilling C, Falke JJ (2008) Molecular mechanism of an oncogenic mutation that alters membrane targeting: Glu17Lys modifies the PIP lipid specificity of the AKT1 PH domain. Biochemistry 47(47):12260-12269.
12. Hussain K, et al. (2011) An activating mutation of AKT2 and human hypoglycemia. Science 334(6055):474.
13. Lindhurst MJ, et al. (2011) A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N Engl J Med 365(7):611-619.
14. Lee JH, et al. (2012) De novo somatic mutations in components of the PI3K-AKT3- mTOR pathway cause hemimegalencephaly. Nat Genet 44(8):941-945.
15. Calleja V, et al. (2007) Intramolecular and intermolecular interactions of protein kinase B define its activation in vivo. PLoS Biol 5(4):e95.
16. Calleja V, Laguerre M, Parker PJ, Larijani B (2009) Role of a novel PH-kinase domain interface in PKB/Akt regulation: Structural mechanism for allosteric inhibition. PLoS Biol 7(1):e17.
17. Wu WI, et al. (2010) Crystal structure of human AKT1 with an allosteric inhibitor reveals a new mode of kinase inhibition. PLoS One 5(9):e12913.
18. Warmuth M, Kim S, Gu XJ, Xia G, Adrián F (2007) Ba/F3 cells and their use in kinase drug discovery. Curr Opin Oncol 19(1):55-60.
19. Mansour SJ, et al. (1994) Transformation of mammalian cells by constitutively active MAP kinase kinase. Science 265(5174):966-970.
20. Boehm JS, et al. (2007) Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell 129(6):1065-1079.
21. Robinson JP, et al. (2011) Activated MEK cooperates with Ink4a/Arf loss or Akt activation to induce gliomas in vivo. Oncogene 30(11):1341-1350.
22. Warfel NA, Niederst M, Newton AC (2011) Disruption of the interface between the pleckstrin homology (PH) and kinase domains of Akt protein is sufficient for hydrophobic motif site phosphorylation in the absence of mTORC2. J Biol Chem 286(45):39122-39129.
23. Bamford S, et al. (2004) The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer 91(2):355-358.
24. Parsons DW, et al. (2005) Colorectal cancer: Mutations in a signalling pathway. Nature 436(7052):792.
25. Greenman C, et al. (2007) Patterns of somatic mutation in human cancer genomes. Nature 446(7132):153-158.
26. Anonymous; Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455(7216):1061-1068.
27. Ding L, et al. (2008) Somatic mutations affect key pathways in lung adenocarcinoma. Nature 455(7216):1069-1075.
28. Kan Z, et al. (2010) Diverse somatic mutation patterns and pathway alterations in human cancers. Nature 466(7308):869-873.
29. Debnath J, Muthuswamy SK, Brugge JS (2003) Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 30(3):256-268.
30. Debnath J, Walker SJ, Brugge JS (2003) Akt activation disrupts mammary acinar architecture and enhances proliferation in an mTOR-dependent manner. J Cell Biol 163(2):315-326.
31. Falke JJ (2007) Membrane recruitment as a cancer mechanism: A case study of Akt PH domain. Cellscience 4(2):25-30.
32. Ding Z, et al. (2010) Physical association of PDK1 with AKT1 is sufficient for pathway activation independent of membrane localization and phosphatidylinositol 3 kinase. PLoS One 5(3):e9910.
33. Davies MA, et al. (2008) A novel AKT3 mutation in melanoma tumours and cell lines. Br J Cancer 99(8):1265-1268.
34. Horn S, et al. (2008) Mutations in the catalytic subunit of class IA PI3K confer leukemogenic potential to hematopoietic cells. Oncogene 27(29):4096-4106.
35. Jaiswal BS, et al. (2009) Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation. Cancer Cell 16(6):463-474.
36. Pal SK, Reckamp K, Yu H, Figlin RA (2010) Akt inhibitors in clinical development for the treatment of cancer. Expert Opin Investig Drugs 19(11):1355-1366.
37. Mattmann ME, Stoops SL, Lindsley CW (2011) Inhibition of Akt with small molecules and biologics: Historical perspective and current status of the patent landscape. Expert Opin Ther Pat 21(9):1309-1338.
38. Barnett SF, et al. (2005) Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors. Biochem J 385(Pt 2):399-408.
39. Lindsley CW, Barnett SF, Layton ME, Bilodeau MT (2008) The PI3K/Akt pathway: Recent progress in the development of ATP-competitive and allosteric Akt kinase inhibitors. Curr Cancer Drug Targets 8(1):7-18.
40. Calleja V, Laguerre M, Larijani B (2009) 3-D structure and dynamics of protein kinase B-new mechanism for the allosteric regulation of an AGC kinase. J Chem Biol 2(1):11-25.
41. Bencsik JR, et al. (2010) Discovery of dihydrothieno- and dihydrofuropyrimidines as potent pan Akt inhibitors. Bioorg Med Chem Lett 20(23):7037-7041.
42. Rhodes N, et al. (2008) Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity. Cancer Res 68(7):2366-2374.
43. Lindsley CW, et al. (2005) Allosteric Akt (PKB) inhibitors: Discovery and SAR of isozyme selective inhibitors. Bioorg Med Chem Lett 15(3):761-764.
44. Pufall MA, Graves BJ (2002) Autoinhibitory domains: Modular effectors of cellular regulation. Annu Rev Cell Dev Biol 18:421-462.
45. Tartaglia M, et al. (2001) Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 29(4):465-468.
46. Tartaglia M, et al. (2003) Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 34(2):148-150.
47. Smith KM, Yacobi R, Van Etten RA (2003) Autoinhibition of Bcr-Abl through its SH3 domain. Mol Cell 12(1):27-37.
48. Levine RL, et al. (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7(4):387-397.