Signalling through Class I PI3Ks in mammalian cells
Abstract
It is now accepted that activation of Class I PI3Ks (phosphoinositide 3-kinases) is one of the most important signal transduction pathways used by cell-surface receptors to control intracellular events. The receptors which access this pathway include those that recognize growth factors, hormones, antigens and inflammatory stimuli, and the cellular events known to be regulated include cell growth, survival, proliferation and movement. We have learnt a great deal about the family of Class I PI3K enzymes themselves and the structural adaptations which allow a variety of cell-surface receptors to regulate their activity. Class I PI3Ks synthesize the phospholipid PtdIns(3,4,5)P3 in the membranes in which they are activated, and it is now accepted that PtdIns(3,4,5)P3 and its dephosphorylation product PtdIns(3,4)P2 are messenger molecules which regulate the localization and function of multiple effectors by binding to their specific PH (pleckstrin homology) domains. The number of direct PtdIns(3,4,5)P3/PtdIns(3,4)P2 effectors which exist, even within a single cell, creates an extremely complex signalling web downstream of PI3K activation. Some key players are beginning to emerge, however, linking PI3K activity to specific cellular responses. These include small GTPases for the Rho and Arf families which regulate the cytoskeletal and membrane rearrangements required for cell movement, and PKB (protein kinase B), which has important regulatory inputs into the regulation of cell-cycle…
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Some evidence puts class IA PI3Ks, at least in part, upstream of Vav and Rac.
“Although the exact position of PI3K␦ relative to other components within the BCR signalosome is still controversial, some evidence puts class IA PI3Ks, at least in part, upstream of Vav and Rac (58).”
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Imidazo[4,5-c]quinolines as inhibitors of the PI3K/PKB-pathway
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Regulation and roles of PI3Kβ, a major actor in platelet signaling and functions
Gratacap, M., Guillermet‐Guibert, J., Martin, V., Chicanne, G., Tronchère, H., Gaits‐Iacovoni, F., & Payrastre, B. (2010) · Advances in Enzyme Regulation · doi:10.1016/j.advenzreg.2010.09.011 · Cited by 86 · see citing works
The PI3K p110δ Regulates Expression of CD38 on Regulatory T Cells
Patton, D. T., Wilson, M. D., Rowan, W. C., Soond, D. R., & Okkenhaug, K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017359 · Cited by 86 · see citing works
Kreis, P., Leondaritis, G., Lieberam, I., & Eickholt, B. J. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00023 · Cited by 85 · see citing works
PI3Kδ and PI3Kγ as Targets for Autoimmune and Inflammatory Diseases
Cushing, T. D., Metz, D. P., Whittington, D. A., & McGee, L. R. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300847w · Cited by 85 · see citing works
- Authors
- Hawkins, P. T., Anderson, K. E., Davidson, K., & Stephens, L. R.
- Affiliations
- Babraham Institute (GB)
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2006-10-01
- Volume
- 34
- Issue
- 5
- Pages
- 647-662
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- OpenAlex
- W1988224683
- Cited by
- 540
- References
- 89
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 10 · 2023: 11 · 2022: 17 · 2021: 20 · 2020: 14 · 2019: 14 · 2018: 21 · 2017: 21 · 2016: 24 · 2015: 19 · 2014: 34 · 2013: 33 · 2012: 48
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Society Transactions (publishedVersion)
- PubMed (publishedVersion)
- 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 › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- class I PI3K, phosphatidylinositol 3,4,5-trisphosphate, PtdIns(3,4)P2, pleckstrin homology domain, cell surface receptors, small GTPases, Akt, cell growth and proliferation, cell survival, oncogenes, PTEN, PI3K isoforms, PI3K inhibitors, transgenic mouse model
- MeSH terms
- Animals, Cell Division, Cell Movement, Cell Survival, Mammals, Models, Biological, Phosphatidylinositols, Receptors, Cell Surface, Signal Transduction, GTP Phosphohydrolases, Carboxylesterase
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