The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
Abstract
Phosphatidylinositol 3-kinases (PI3Ks) evolved from a single enzyme that regulates vesicle trafficking in unicellular eukaryotes into a family of enzymes that regulate cellular metabolism and growth in multicellular organisms. In this review, we examine how the PI3K pathway has evolved to control these fundamental processes, and how this pathway is in turn regulated by intricate feedback and crosstalk mechanisms. In light of the recent advances in our understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, we discuss the exciting therapeutic opportunities for targeting this pathway to treat these diseases.
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mTORC1 appears to be critical for linking PI3K signaling with tumor metabolism.
“mTORC1 appears to be critical for linking PI3K signaling with tumor metabolism (16, 59, 60).”
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- Authors
- Engelman, J. A., Luo, J., & Cantley, L. C.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Cantley, Lewis C.
- Venue
- Nature Reviews Genetics
- Published
- 2006-08
- Volume
- 7
- Issue
- 8
- Pages
- 606-619
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- OpenAlex
- W2009886463
- Cited by
- 3,330
- References
- 14
- Citations by year
- 2026: 72 · 2025: 129 · 2024: 170 · 2023: 174 · 2022: 174 · 2021: 193 · 2020: 186 · 2019: 162 · 2018: 146 · 2017: 179 · 2016: 170 · 2015: 198 · 2014: 233 · 2013: 205 · 2012: 216
- FWCI
- 9.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Genetics (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, lipid kinase, vesicle trafficking, cellular metabolism, cell growth regulation, feedback regulation, signaling crosstalk, diabetes mellitus, cancer, PI3K inhibitors
- MeSH terms
- Animals, Cells, Multigene Family, Humans, Evolution, Molecular, Phosphatidylinositol 3-Kinases, Cell Growth Processes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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