A biochemical mechanism for the oncogenic potential of the p110β catalytic subunit of phosphoinositide 3-kinase

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

Volumn 107, Issue 46, 2010, Pages 19897-19902

  Dbouk, Hashem A ^a   Pang, Huan ^a   Fiser, Andras ^a   Backer, Jonathan M ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Lipid kinase; Oncogenic mutation; Oncogenic transformation

Indexed keywords

ISOPROTEIN; MUTANT PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN P110; PROTEIN P110 BETA; PROTEIN P110 DELTA; PROTEIN P85; S6 KINASE; UNCLASSIFIED DRUG;

BIOCHEMISTRY; CELL STRAIN 3T3; CONFERENCE PAPER; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME REGULATION; HUMAN; HYDROGEN BOND; IN VITRO STUDY; PRIORITY JOURNAL; SEQUENCE ANALYSIS; WILD TYPE;

EID: 78650529784     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1008739107     Document Type: Article

References (33)

1. 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.
2. Yuan TL, Cantley LC (2008) PI3K pathway alterations in cancer: Variations on a theme. Oncogene 27:5497-5510.
3. 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.
4. Kurosu H, et al. (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.
5. Guillermet-Guibert J, et al. (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.
6. Wu H, Yan Y, Backer JM (2007) Regulation of class IA PI3Ks. Blochem Soc Trans 35: 242-244.
7. Miled N, et al. (2007) Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science 317:239-242.
8. Huang CH, et al. (2007) The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science 318:1744-1748.
9. Mandelker D, et al. (2009) A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane. Proc Natl Acad Sci USA 106: 16996-17001.
10. Yu J, et al. (1998) Regulation of the p85/p110 phosphatidylinositol 3'-kinase: Stabilization and inhibition of the p110alpha catalytic subunit by the p85 regulatory subunit. Mol Cell Biol 18:1379-1387.
11. Wu H, et al. (2009) Regulation of Class IA PI 3-kinases: C2 domain-iSH2 domain contacts inhibit p85/p110alpha and are disrupted in oncogenic p85 mutants. Proc Natl Acad Sci USA 106:20258-20263.
12. Liu P, Cheng H, Roberts TM, Zhao JJ (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Dlscov 8:627-644.
13. Bénistant C, Chapuis H, Roche S (2000) A specific function for phosphatidylinositol 3-kinase alpha (p85alpha-p110alpha) in cell survival and for phosphatidylinositol 3-kinase beta (p85alpha-p110beta) in de novo DNA synthesis of human colon carcinoma cells. Oncogene 19:5083-5090.
14. Knobbe CB, Reifenberger G (2003) Genetic alterations and aberrant expression of genes related to the phosphatidyl-inositol-3'-kinase/protein kinase B (Akt) signal transduction pathway in glioblastomas. Brain Pathol 13:507-518.
15. 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.
16. Jimenez C, et al. (1998) Identification and characterization of a new oncogene derived from the regulatory subunit of phosphoinositide 3-kinase. EMBO J 17:743-753.
17. Shekar SC, et al. (2005) Mechanism of constitutive phosphoinositide 3-kinase activation by oncogenic mutants of the p85 regulatory subunit. J Biol Chem 280: 27850-27855.
18. Jaiswal BS, et al. (2009) Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation. Cancer Cell 16:463-474.
19. Yip SC, et al. (2004) Over-expression of the p110beta but not p110alpha isoform of PI 3-kinase inhibits motility in breast cancer cells. Cell Motil Cytoskeleton 59:180-188.
20. Amzel LM, et al. (2008) Structural comparisons of class I phosphoinositide 3-kinases. Nat Rev Cancer 8:665-669.
21. Berndt A, et al. (2010) The p110delta structure: Mechanisms for selectivity and potency of new PI(3)K inhibitors. Nat Chem Biol 6:117-124.
22. Wee S, et al. (2008) PTEN-deficient cancers depend on PIK3CB. Proc Natl Acad Sci USA 105:13057-13062.
23. Jia S, et al. (2008) Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature 454:776-779.
24. Ciraolo E, et al. (2008) Phosphoinositide 3-kinase p110beta activity: Key role in metabolism and mammary gland cancer but not development. Sci Signal, 10.1126/scisignal.1161577.
25. Hill KM, et al. (2010) The role of PI 3-kinase p110beta in AKT signally, cell survival, and proliferation in human prostate cancer cells. Prostate 70:755-764.
26. Sun M, Hillmann P, Hofmann BT, Hart JR, Vogt PK (2010) Cancer-derived mutations in the regulatory subunit p85α of phosphoinositide 3-kinase function through the catalytic subunit p110α. Proc Natl Acad Sci USA 107:15547-15552.
27. Maier U, Babich A, Nürnberg B (1999) Roles of non-catalytic subunits in gbetagammainduced activation of class I phosphoinositide 3-kinase isoforms β and gamma. J Biol Chem 274:29311-29317.
28. Fiser A, Sali A (2003) Modeller: Generation and refinement of homology-based protein structure models. Methods Enzymol 374:461-491.
29. Collaborative Computational Project, Number 4 (1994) The CCP4 suite: Programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50:760-763.
30. Fernandez-Fuentes N, Rai BK, Madrid-Aliste CJ, Fajardo JE, Fiser A (2007) Comparative protein structure modeling by combining multiple templates and optimizing sequence-to-structure alignments. Bioinformatics 23:2558-2565.
31. Rai BK, Madrid-Aliste CJ, Fajardo JE, Fiser A (2006) MMM: A sequence-to-structure alignment protocol. Bioinformatics 22:2691-2692.
32. Rai BK, Fiser A (2006) Multiple mapping method: A novel approach to the sequence- to-structure alignment problem in comparative protein structure modeling. Proteins 63:644-661.
33. Sippl MJ (1993) Recognition of errors in three-dimensional structures of proteins. Proteins 17:355-362.