The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation
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The Ras-extracellular signal-regulated kinase (Ras-ERK) and phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR) signaling pathways are the chief mechanisms for controlling cell survival, differentiation, proliferation, metabolism, and motility in response to extracellular cues. Components of these pathways were among the first to be discovered when scientists began cloning proto-oncogenes and purifying cellular kinase activities in the 1980s. Ras-ERK and PI3K-mTOR were originally modeled as linear signaling conduits activated by different stimuli, yet even early experiments hinted that they might intersect to regulate each other and co-regulate downstream functions. The extent of this cross-talk and its significance in cancer therapeutics are now becoming clear.
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ERK signaling feeds into several nodes of PI3K/mTOR, such as phosphorylation of TSC2.
“An additional layer of complexity is the cross-regulation between the two pathways with ERK signaling feeding into several nodes of PI3K/mTOR such as its phosphorylation of TSC236–38.”
From Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer (2024) · cites this paper as [36]
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- Authors
- Mendoza, M. C., Er, E. E., & Blenis, J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Blenis, John
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 36
- Issue
- 6
- Pages
- 320-328
- ISSN
- 0968-0004 (ISSN-L)
- PMC
- PMC3112285
- OpenAlex
- W1998203489
- Cited by
- 1,817
- References
- 103
- Citations by year
- 2026: 112 · 2025: 96 · 2024: 122 · 2023: 133 · 2022: 127 · 2021: 163 · 2020: 166 · 2019: 164 · 2018: 144 · 2017: 158 · 2016: 123 · 2015: 100 · 2014: 92 · 2013: 55 · 2012: 49
- FWCI
- 5.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- LAM Foundation
- Susan G. Komen
- National Cancer Institute (R37CA046595)
- National Institute of General Medical Sciences (R01GM051405)
- 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
- Ras/ERK signaling pathway, signaling crosstalk, cell survival, cell proliferation, cell differentiation, cellular metabolism, cell motility, proto-oncogenes, cancer therapeutics
- MeSH terms
- Humans, Signal Transduction, ras Proteins, Extracellular Signal-Regulated MAP Kinases, Phosphatidylinositol 3-Kinase, TOR Serine-Threonine Kinases
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