The phosphoinositide 3-kinase pathway
Abstract
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.
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Activation of phosphoinositide-3-kinase by ligation of growth factors to their cellular receptors promotes recruitment of Akt to the plasma membrane and its subsequent activation.
“Activation of phosphoinositide-3-kinase (PI3K) by ligation of growth factors to their cellular receptors promotes recruitment of Akt to the plasma membrane and its subsequent activation 28.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [28]
Cites
Fruman, D. A., Meyers, R., & Cantley, L. C. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.481 · Cited by 1,261 · see citing works
Self-citationBrunet, A., Datta, S. R., & Greenberg, M. E. (2001) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00211-7 · Cited by 1,193 · see citing works
Lawlor, M. A., & Alessi, D. R. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.16.2903 · Cited by 1,071 · see citing works
Regulation of C. elegans Life-Span by Insulinlike Signaling in the Nervous System
Wolkow, C. A., Kimura, K. D., Lee, M. S., & Ruvkun, G. (2000) · Science · doi:10.1126/science.290.5489.147 · Cited by 681 · see citing works
PTEN: a tumour suppressor that functions as a phospholipid phosphatase
Maehama, T. (1999) · Trends in Cell Biology · doi:10.1016/s0962-8924(99)01519-6 · Cited by 591 · see citing works
Clark, A. S., West, K. A., Streicher, S. A., & Dennis, P. A. (2002) · PubMed · Cited by 589 · see citing works
The lipid phosphatase SHIP2 controls insulin sensitivity
Clément, S., Krause, U., Desmedt, F., Tanti, J., Behrends, J., Pesesse, X., Sasaki, T., Penninger, J. M., Doherty, M., Malaisse, W. J., et al. (2001) · Nature · doi:10.1038/35051094 · Cited by 377 · see citing works
Identification of CISK, a new member of the SGK kinase family that promotes IL-3-dependent survival
Liu, D., Xiao-hong, Y., & Songyang, Z. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00733-8 · Cited by 135 · see citing works
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Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598 · see citing works
Mechanisms of type-I- and type-II-interferon-mediated signalling
Platanias, L. C. (2005) · Nature reviews. Immunology · doi:10.1038/nri1604 · Cited by 3,480 · see citing works
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
Engelman, J. A., Luo, J., & Cantley, L. C. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1879 · Cited by 3,330 · see citing works
Self-citationAerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057 · see citing works
Routes and mechanisms of extracellular vesicle uptake
Mulcahy, L. A., Pink, R. C., & Carter, D. R. F. (2014) · Journal of Extracellular Vesicles · doi:10.3402/jev.v3.24641 · Cited by 2,832 · see citing works
Zhou, Y., Wang, J., Gu, Z., Wang, S., Zhu, W., Aceña, J. L., Soloshonok, V. A., Izawa, K., & Liu, H. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00392 · Cited by 2,824 · see citing works
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Di Paolo, G., & De Camilli, P. (2006) · Nature · doi:10.1038/nature05185 · Cited by 2,790 · see citing works
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Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445 · see citing works
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Ryter, S. W., Alam, J., & Choi, A. M. K. (2006) · Physiological Reviews · doi:10.1152/physrev.00011.2005 · Cited by 2,308 · see citing works
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Yu, H., & Jove, R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1275 · Cited by 2,278 · see citing works
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Wang, Y., Branicky, R. S., Noë, A., & Hekimi, S. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201708007 · Cited by 2,199 · see citing works
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Glaviano, A., Foo, A. S. C., Lam, H. Y., Yap, K. C. H., Jacot, W., Jones, R. H., Eng, H., Nair, M. G., Makvandi, P., Geoerger, B., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01827-6 · Cited by 2,138 · see citing works
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Lonze, B. E., & Ginty, D. D. (2002) · Neuron · doi:10.1016/s0896-6273(02)00828-0 · Cited by 2,127 · see citing works
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He, Y., Sun, M., Zhang, G. G., Yang, J., Chen, K. S., Xu, W. W., & Li, B. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00828-5 · Cited by 1,996 · see citing works
Stitt, T. N., Drujan, D., Clarke, B. A., Panaro, F., Timofeyva, Y., Kline, W. O., Gonzalez, M., Yancopoulos, G. D., & Glass, D. J. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00211-4 · Cited by 1,964 · see citing works
Nagata, Y., Lan, K.-H., Zhou, X., Tan, M., Esteva, F. J., Sahin, A. A., Klos, K. S., Li, P., Monia, B. P., Nguyen, N. T., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.022 · Cited by 1,858 · see citing works
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Ravikumar, B., Sarkar, S., Davies, J. E., Futter, M., Garcı́a-Arencibia, M., Green-Thompson, Z. W., Jiménez-Sánchez, M., Korolchuk, V. I., Lichtenberg, M., Luo, S., et al. (2010) · Physiological Reviews · doi:10.1152/physrev.00030.2009 · Cited by 1,726 · see citing works
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Frey, N., & Olson, E. N. (2003) · Annual Review of Physiology · doi:10.1146/annurev.physiol.65.092101.142243 · Cited by 1,458 · see citing works
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Lemmon, M. A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2328 · Cited by 1,455 · see citing works
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Brugarolas, J., Lei, K., Hurley, R. L., Manning, B. D., Reiling, J. H., Hafen, E., Witters, L. A., Ellisen, L. W., & Kaelin, W. G. (2004) · Genes & Development · doi:10.1101/gad.1256804 · Cited by 1,384 · see citing works
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Luo, J., Manning, B. D., & Cantley, L. C. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00248-4 · Cited by 1,290 · see citing works
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Fingar, D. C., & Blenis, J. (2004) · Oncogene · doi:10.1038/sj.onc.1207542 · Cited by 1,250 · see citing works
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Courtney, K. D., Corcoran, R. B., & Engelman, J. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.25.3641 · Cited by 1,235 · see citing works
Chang, F., Lee, J. T., Navolanic, P. M., Steelman, L. S., Shelton, J. G., Blalock, W. L., Franklin, R. A., & McCubrey, J. A. (2003) · Leukemia · doi:10.1038/sj.leu.2402824 · Cited by 1,176 · see citing works
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Wu, Y.-T., Tan, H.-L., Shui, G., Bauvy, C., Huang, Q., Wenk, M. R., Ong, C.-N., Codogno, P., & Shen, H.-M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.080796 · Cited by 1,127 · see citing works
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Harrington, L. S., Findlay, G. M., Gray, A., Толкачева, Т. А., Wigfield, S., Rebholz, H., Barnett, J., Leslie, N. R., Cheng, S., Shepherd, P. R., et al. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200403069 · Cited by 1,123 · see citing works
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Zhu, J., & Thompson, C. B. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0123-5 · Cited by 1,106 · see citing works
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Kim, J.-A., Wei, Y., & Sowers, J. R. (2008) · Circulation Research · doi:10.1161/circresaha.107.165472 · Cited by 1,103 · see citing works
Martin, M., Rehani, K., Jope, R. S., & Michalek, S. M. (2005) · Nature Immunology · doi:10.1038/ni1221 · Cited by 1,080 · see citing works
Principles of Tumor Suppression
Sherr, C. J. (2004) · Cell · doi:10.1016/s0092-8674(03)01075-4 · Cited by 1,028 · see citing works
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Guo, X., & Wang, X. (2008) · Cell Research · doi:10.1038/cr.2008.302 · Cited by 1,027 · see citing works
Holmes, K., Roberts, O. L., Thomas, A. M., & Cross, M. J. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.05.013 · Cited by 1,020 · see citing works
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Baehrecke, E. H. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1666 · Cited by 986 · see citing works
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Androutsellis‐Theotokis, A., Leker, R. R., Soldner, F., Hoeppner, D. J., Ravin, R., Poser, S., Rueger, M. A., Bae, S., Kittappa, R., & McKay, R. D. G. (2006) · Nature · doi:10.1038/nature04940 · Cited by 952 · see citing works
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Stommel, J. M., Kimmelman, A. C., Ying, H., Nabioullin, R., Ponugoti, A. H., Wiedemeyer, R., Stegh, A. H., Bradner, J. E., Ligon, K. L., Brennan, C., et al. (2007) · Science · doi:10.1126/science.1142946 · Cited by 938 · see citing works
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Samuels, Y., Diaz, L. A., Schmidt-Kittler, O., Cummins, J. M., DeLong, L., Cheong, I., Rago, C., Huso, D. L., Lengauer, C., Kinzler, K. W., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.014 · Cited by 915 · see citing works
Bernardo, B. C., Weeks, K. L., Pretorius, L., & McMullen, J. R. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.04.005 · Cited by 892 · see citing works
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Koivusalo, M., Welch, C. M., Hayashi, H., Scott, C. C., Kim, M., Alexander, T. R., Touret, N., Hahn, K. M., & Grinstein, S. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200908086 · Cited by 878 · see citing works
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Muniyappa, R., Montagnani, M., Koh, K. K., & Quon, M. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0006 · Cited by 873 · see citing works
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McLaughlin, S., & Murray, D. (2005) · Nature · doi:10.1038/nature04398 · Cited by 868 · see citing works
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Reddy, P., Liu, L., Adhikari, D., Jagarlamudi, K., Singareddy, R., Shen, Y., Du, C., Tang, W., Hämäläinen, T. M., Peng, S. L., et al. (2008) · Science · doi:10.1126/science.1152257 · Cited by 854 · see citing works
Frey, N., Katus, H. A., Olson, E. N., & Hill, J. A. (2004) · Circulation · doi:10.1161/01.cir.0000120390.68287.bb · Cited by 845 · see citing works
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Sullivan, L. B., & Chandel, N. S. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-17 · Cited by 799 · see citing works
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Bader, A. G., Kang, S., Zhao, L., & Vogt, P. K. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1753 · Cited by 795 · see citing works
Serra, V., Markman, B., Scaltriti, M., Eichhorn, P. J. A., Valero, V., Guzman, M., Botero, M. L., Llonch, E., Atzori, F., Di Cosimo, S., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1385 · Cited by 787 · see citing works
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Yu, L., Wei, J., & Liu, P. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.06.019 · Cited by 785 · see citing works
PI 3-kinase, Akt and cell survival
Downward, J. (2004) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2004.01.002 · Cited by 783 · see citing works
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Polivka, J., & Janku, F. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.12.004 · Cited by 765 · see citing works
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Castellano, E., & Downward, J. (2011) · Genes & Cancer · doi:10.1177/1947601911408079 · Cited by 762 · see citing works
Folkes, A. J., Ahmadi, K., ALDERTON, W. K., Alix, S., Baker, S. J., Box, G., Chuckowree, I., Clarke, P. A., Depledge, P., Eccles, S. A., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm800295d · Cited by 756 · see citing works
Ubiquitination regulates PTEN nuclear import and tumor suppression
Trotman, L. C., Wang, X., Alimonti, A., Chen, Z., Teruya-Feldstein, J., Yang, H., Pavletich, N. P., Carver, B. S., Cordon-Cardo, C., Erdjument-Bromage, H., et al. (2007) · Cell · doi:10.1016/j.cell.2006.11.040 · Cited by 748 · see citing works
Ca2+ signalling checkpoints in cancer: remodelling Ca2+ for cancer cell proliferation and survival
Roderick, H. L., & Cook, S. J. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2374 · Cited by 731 · see citing works
Activation of Platelet Function Through G Protein–Coupled Receptors
Offermanns, S. (2006) · Circulation Research · doi:10.1161/01.res.0000251742.71301.16 · Cited by 725 · see citing works
Regulation of glucose homeostasis by glucocorticoids
Kuo, T., McQueen, A., Chen, T.-C., & Wang, J.-C. (2015) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-2895-8_5 · Cited by 723 · see citing works
Mammalian target of rapamycin: a central node of complex signaling cascades.
Dobashi, Y., Watanabe, Y., Miwa, C., Suzuki, S., & Koyama, S. (2011) · PubMed Central · Cited by 721 · see citing works
Bendell, J. C., Rodon, J. A., Burris, H. A., de Jonge, M. J. A., Verweij, J., Birle, D. C., Demanse, D., Buck, S. S. D., Ru, Q. C., Peters, M., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.36.1360 · Cited by 687 · see citing works
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Steelman, L. S., Pohnert, S. C., Shelton, J. G., Franklin, R. A., Bertrand, F. E., & McCubrey, J. A. (2004) · Leukemia · doi:10.1038/sj.leu.2403241 · Cited by 681 · see citing works
The E3 Ligase TRAF6 Regulates Akt Ubiquitination and Activation
Yang, W., Wang, J., Chan, C., Lee, S.-W., Campos, A. D., Lamothe, B., Hur, L., Grabiner, B. C., Lin, X., Darnay, B. G., et al. (2009) · Science · doi:10.1126/science.1175065 · Cited by 669 · see citing works
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Shorning, B. Y., Dass, M. S., Smalley, M. J., & Pearson, H. B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124507 · Cited by 638 · see citing works
Diffuse glioma growth: a guerilla war
Claes, A., Idema, A. J. S., & Wesseling, P. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0293-7 · Cited by 627 · see citing works
Jackson, S. P., Darbousset, R., & Schoenwaelder, S. M. (2019) · Blood · doi:10.1182/blood-2018-11-882993 · Cited by 625 · see citing works
Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance
Yang, X., Ongusaha, P. P., Miles, P. D. G., Havstad, J. C., Zhang, F., So, W. V., Kudlow, J. E., Michell, R. H., Olefsky, J. M., Field, S. J., et al. (2008) · Nature · doi:10.1038/nature06668 · Cited by 617 · see citing works
Redox regulation of PI 3‐kinase signalling via inactivation of PTEN
Leslie, N. R., Bennett, D., Lindsay, Y. E., Stewart, H., Gray, A., & Downes, C. P. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg513 · Cited by 614 · see citing works
Puig, Ó., Marr, M. T., Ruhf, M.-L., & Tjian, R. (2003) · Genes & Development · doi:10.1101/gad.1098703 · Cited by 612 · see citing works
Insulin resistance and cancer risk: An overview of the pathogenetic mechanisms
Arcidiacono, B., Iiritano, S., Nocera, A., Possidente, K., Nevolo, M. T., Ventura, V., Foti, D., Chiefari, E., & Brunetti, A. (2012) · Experimental Diabetes Research · doi:10.1155/2012/789174 · Cited by 606 · see citing works
The Two Faces of Reactive Oxygen Species in Cancer
Reczek, C. R., & Chandel, N. S. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-041916-065808 · Cited by 602 · see citing works
“Thus, the ROS-induced PI3K/Akt survival pathway has been shown to be activated in a majority of cancers (Cantley 2002).”
BackgroundHippocampal Neuronal Polarity Specified by Spatially Localized mPar3/mPar6 and PI 3-Kinase Activity
Shi, S.-H., Jan, L. Y., & Jan, Y.-N. (2003) · Cell · doi:10.1016/s0092-8674(02)01249-7 · Cited by 600 · see citing works
Phosphorylation of IRS proteins, insulin action, and insulin resistance
Boura-Halfon, S., & Zick, Y. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90437.2008 · Cited by 598 · see citing works
Class I PI3K in oncogenic cellular transformation
Zhao, L., & Vogt, P. K. (2008) · Oncogene · doi:10.1038/onc.2008.244 · Cited by 598 · see citing works
Jünger, M. A., Rintelen, F., Stocker, H., Wasserman, J. D., Végh, M., Radimerski, T., Greenberg, M. E., & Hafen, E. (2003) · Journal of Biology · doi:10.1186/1475-4924-2-20 · Cited by 595 · see citing works
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- Authors
- Cantley, L. C.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Cantley, Lewis C.
- ORCID
- Cantley, Lewis C.
- Venue
- Science
- Published
- 2002-05-31
- Volume
- 296
- Issue
- 5573
- Pages
- 1655-1657
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2070732456
- Cited by
- 5,621
- References
- 9
- Citations by year
- 2026: 87 · 2025: 137 · 2024: 134 · 2023: 182 · 2022: 200 · 2021: 203 · 2020: 216 · 2019: 215 · 2018: 232 · 2017: 276 · 2016: 243 · 2015: 297 · 2014: 292 · 2013: 306 · 2012: 325
- FWCI
- 76.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM041890)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- phosphatidylinositol 3-kinase, PI3K signaling, phosphatidylinositol 3,4,5-trisphosphate, cell survival signaling, gene expression regulation, cellular metabolism, cytoskeletal rearrangement, diabetes mellitus, cancer, therapeutic target
- MeSH terms
- Animals, Cell Membrane, Cell Physiological Phenomena, Diabetes Mellitus, Type 2, Humans, Models, Biological, Neoplasms, Phosphorylation, Protein Kinases, Proto-Oncogene Proteins, Signal Transduction, Protein Serine-Threonine Kinases, Phosphatidylinositol Phosphates, Phosphatidylinositol 4,5-Diphosphate, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, 3-Phosphoinositide-Dependent Protein Kinases
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