Effects of oncogenic p110α subunit mutations on the lipid kinase activity of phosphoinositide 3-kinase
作者： Jeffrey D. Carson , Glenn Van Aller , Ruth Lehr , Robert H. Sinnamon , Robert B. Kirkpatrick
DOI: 10.1042/BJ20070681
关键词:
摘要: The PIK3CA gene, encoding the p110α catalytic subunit of Class IA PI3Ks (phosphoinositide 3-kinases), is frequently mutated in many human tumours. three most common tumour-derived alleles p110α, H1047R, E542K and E545K, were shown to potently activate PI3K signalling epithelial cells. In present study, we examine biochemical activity recombinantly purified oncogenic mutants. kinetic characterizations wt (wild-type) ‘hot spot’ mutants show that all have approx. 2-fold increase lipid kinase activities. Interestingly, phosphorylated IRS-1 (insulin receptor substrate-1) protein shows activation for H1047R but not E545K PI3Kα, suggesting these mutations represent different mechanisms hence transforming cancer
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biochemj.org参考文章(28)
J.M. Backer, M.G. Myers, X.J. Sun, D.J. Chin, S.E. Shoelson, M. Miralpeix, M.F. White, Association of IRS-1 with the insulin receptor and the phosphatidylinositol 3'-kinase. Formation of binary and ternary signaling complexes in intact cells. Journal of Biological Chemistry. ,vol. 268, pp. 8204- 8212 ,(1993) , 10.1016/S0021-9258(18)53083-0
Tamara Rordorf-Nikolic, Debra J. Van Horn, Daxin Chen, Morris F. White, Jonathan M. Backer, Regulation of Phosphatidylinositol 3′-Kinase by Tyrosyl Phosphoproteins FULL ACTIVATION REQUIRES OCCUPANCY OF BOTH SH2 DOMAINS IN THE 85-kDa REGULATORY SUBUNIT Journal of Biological Chemistry. ,vol. 270, pp. 3662- 3666 ,(1995) , 10.1074/JBC.270.8.3662
Nicholas Gerard Byrne, David Geraint Owen, High throughput screen ,(1999)
Kurt R. Auger, Leslie A. Serunian, Stephen P. Soltoff, Peter Libby, Lewis C. Cantley, PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells Cell. ,vol. 57, pp. 167- 175 ,(1989) , 10.1016/0092-8674(89)90182-7
Daniel Morgensztern, Howard L. McLeod, PI3K/Akt/mTOR pathway as a target for cancer therapy. Anti-Cancer Drugs. ,vol. 16, pp. 797- 803 ,(2005) , 10.1097/01.CAD.0000173476.67239.3B
S. Chandra Shekar, Haiyan Wu, Zheng Fu, Shu-Chin Yip, Nagajyothi, Sean M. Cahill, Mark E. Girvin, Jonathan M. Backer, Mechanism of Constitutive Phosphoinositide 3-Kinase Activation by Oncogenic Mutants of the p85 Regulatory Subunit Journal of Biological Chemistry. ,vol. 280, pp. 27850- 27855 ,(2005) , 10.1074/JBC.M506005200
M. Gymnopoulos, M.-A. Elsliger, P. K. Vogt, Rare cancer-specific mutations in PIK3CA show gain of function Proceedings of the National Academy of Sciences of the United States of America. ,vol. 104, pp. 5569- 5574 ,(2007) , 10.1073/PNAS.0701005104
H. Wu, Y. Yan, J.M. Backer, Regulation of class IA PI3Ks Biochemical Society Transactions. ,vol. 35, pp. 242- 244 ,(2007) , 10.1042/BST0350242
Andreas G Bader, Sohye Kang, Li Zhao, Peter K Vogt, None, Oncogenic PI3K deregulates transcription and translation. Nature Reviews Cancer. ,vol. 5, pp. 921- 929 ,(2005) , 10.1038/NRC1753
Jinghua Yu, Christina Wjasow, Jonathan M. Backer, Regulation of the p85/p110α Phosphatidylinositol 3′-Kinase Journal of Biological Chemistry. ,vol. 273, pp. 30199- 30203 ,(1998) , 10.1074/JBC.273.46.30199