Cited by 1,817PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingMetabolism, Diabetes, and Cancer

The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation

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Mendoza, Michelle C., Er, E. Emrah, Blenis, John·2011·Trends in Biochemical Sciences

Abstract

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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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)
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
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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