Cited by 556PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingMetabolism, Diabetes, and Cancer

Signalling through Class I PI3Ks in mammalian cells

Hawkins, P.T., Anderson, K.E., Davidson, K., Stephens, L.R.·2006·Biochemical Society Transactions

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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Crossref · 10.1042/bst0340647

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Authors
Hawkins, P. T., Anderson, K. E., Davidson, K., & Stephens, L. R.
Affiliations
Babraham Institute (GB)
Venue
Biochemical Society Transactions
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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