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

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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

DOI 10.1016/j.tibs.2011.03.006PMC PMC3112285

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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
ORCID: Mendoza, Michelle C.
Er, E. Emrah
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)
DOI: 10.1016/j.tibs.2011.03.006
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation

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