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Science 31 May 2002:
Vol. 296. no. 5573, pp. 1655 - 1657
DOI: 10.1126/science.296.5573.1655
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The Phosphoinositide 3-Kinase Pathway

Lewis C. Cantley*

Phosphorylated lipids are produced at cellular membranes during signaling events and contribute to the recruitment and activation of various signaling components. The role of phosphoinositide 3-kinase (PI3K), which catalyzes the production of phosphatidylinositol-3,4,5-trisphosphate, in cell survival pathways; the regulation of gene expression and cell metabolism; and cytoskeletal rearrangements are highlighted. The PI3K pathway is implicated in human diseases including diabetes and cancer, and understanding the intricacies of this pathway may provide new avenues for therapuetic intervention.

Department of Cell Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115-5713, USA.
*   To whom correspondence should be addressed. E-mail: cantley{at}helix.mgh.harvard.edu

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Protein Phosphatase 3 Differentially Modulates Vascular Endothelial Growth Factor- and Fibroblast Growth Factor 2-Stimulated Cell Proliferation and Signaling in Ovine Fetoplacental Artery Endothelial Cells.
K. Wang, Y. Song, D.-B. Chen, and J. Zheng (2008)
Biol Reprod 79, 704-710
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Nerve Growth Factor Inhibits Na+/H+ Exchange and Formula Absorption through Parallel Phosphatidylinositol 3-Kinase-mTOR and ERK Pathways in Thick Ascending Limb.
D. W. Good, T. George, and B. A. Watts III (2008)
J. Biol. Chem. 283, 26602-26611
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The Effects of Common Genetic Variants in Oncogenes on Ovarian Cancer Survival.
L. Quaye, S. A. Gayther, S. J. Ramus, R. A. Di Cioccio, V. McGuire, E. Hogdall, C. Hogdall, J. Blaakr, D. F. Easton, B. A.J. Ponder, et al. (2008)
Clin. Cancer Res. 14, 5833-5839
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PTEN-deficient cancers depend on PIK3CB.
S. Wee, D. Wiederschain, S.-M. Maira, A. Loo, C. Miller, R. deBeaumont, F. Stegmeier, Y.-M. Yao, and C. Lengauer (2008)
PNAS 105, 13057-13062
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Down-regulation of the PI3-kinase/Akt pathway by ERK MAP kinase in growth factor signaling.
H. Hayashi, Y. Tsuchiya, K. Nakayama, T. Satoh, and E. Nishida (2008)
Genes Cells 13, 941-947
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Mechanism of Influenza A Virus NS1 Protein Interaction with the p85{beta}, but Not the p85{alpha}, Subunit of Phosphatidylinositol 3-Kinase (PI3K) and Up-regulation of PI3K Activity.
Y. Li, D. H. Anderson, Q. Liu, and Y. Zhou (2008)
J. Biol. Chem. 283, 23397-23409
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Molecular mechanism of membrane targeting by the GRP1 PH domain,boxs.
J. He, R. M. Haney, M. Vora, V. V. Verkhusha, R. V. Stahelin, and T. G. Kutateladze (2008)
J. Lipid Res. 49, 1807-1815
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PI3K/Akt signaling as a key regulatory pathway for chondrocyte terminal differentiation..
K. Kita, T. Kimura, N. Nakamura, H. Yoshikawa, and T. Nakano (2008)
Genes Cells 13, 839-850
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Class I PI3 Kinase Inhibition by the Pyridinylfuranopyrimidine Inhibitor PI-103 Enhances Tumor Radiosensitivity.
R. Prevo, E. Deutsch, O. Sampson, J. Diplexcito, K. Cengel, J. Harper, P. O'Neill, W. G. McKenna, S. Patel, and E. J. Bernhard (2008)
Cancer Res. 68, 5915-5923
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Class 1A PI3K regulates vessel integrity during development and tumorigenesis.
T. L. Yuan, H. S. Choi, A. Matsui, C. Benes, E. Lifshits, J. Luo, J. V. Frangioni, and L. C. Cantley (2008)
PNAS 105, 9739-9744
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Cancer Cell-Derived Clusterin Modulates the Phosphatidylinositol 3'-Kinase-Akt Pathway through Attenuation of Insulin-Like Growth Factor 1 during Serum Deprivation.
H. Jo, Y. Jia, K. K. Subramanian, H. Hattori, and H. R. Luo (2008)
Mol. Cell. Biol. 28, 4285-4299
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The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization.
F. Fouladkou, T. Landry, H. Kawabe, A. Neeb, C. Lu, N. Brose, V. Stambolic, and D. Rotin (2008)
PNAS 105, 8585-8590
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Insulin-like Growth Factor-I Stimulates Shc-dependent Phosphatidylinositol 3-Kinase Activation via Grb2-associated p85 in Vascular Smooth Muscle Cells.
Y. Radhakrishnan, L. A. Maile, Y. Ling, L. M. Graves, and D. R. Clemmons (2008)
J. Biol. Chem. 283, 16320-16331
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Molecular Signature of MT1-MMP: Transactivation of the Downstream Universal Gene Network in Cancer.
D. V. Rozanov, A. Y. Savinov, R. Williams, K. Liu, V. S. Golubkov, S. Krajewski, and A. Y. Strongin (2008)
Cancer Res. 68, 4086-4096
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