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Cited by 7,929HER2/EGFR in Cancer ResearchProtein Kinase Regulation and GTPase SignalingReceptor Mechanisms and Signaling

Cell Signaling by Receptor Tyrosine Kinases

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Lemmon, Mark A., Schlessinger, Joseph·2010·Cell
DOI 10.1016/j.cell.2010.06.011PMC PMC2914105
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Abstract

Recent structural studies of receptor tyrosine kinases (RTKs) have revealed unexpected diversity in the mechanisms of their activation by growth factor ligands. Strategies for inducing dimerization by ligand binding are surprisingly diverse, as are mechanisms that couple this event to activation of the intracellular tyrosine kinase domains. As our understanding of these details becomes increasingly sophisticated, it provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases. Much remains to be learned, however, about the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses.

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  • HB-EGF is an EGFR ligand, and EGFR often connects extracellular signals to gene expression changes through MAPK signaling.

    “HB-EGF is a ligand for the EGFR, which often links extracellular signals with changes in gene expression via a MAPK signaling pathway”

    From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Lemmon and Schlessinger, 2010

  • The receptor tyrosine kinases TrkA, FGFR2, PDGFR, EGFR, IR, IGF1R and TIE2 are key regulators of cellular processes and are involved in the development and progression of many types of cancer.

    “The receptor tyrosine kinases TrkA, FGFR2, PDGFR, EGFR, IR, IGF1R and TIE2 are key regulators of cellular processes and are involved in the development and progression of many types of cancer28.”

    From Design of protein-binding proteins from the target structure alone (2022) · cites this paper as [28]

  • TGF-β also activates non-Smad pathways including PI3K-Akt-mTOR, Erk MAPK, p38 MAPK, and Rho GTPases, but these are not diagnostic of TGF-β signaling because RTKs strongly activate them.

    “While Smad signaling uniquely defines “canonical” signaling for TGF-β family proteins, TGF-β also activates non-Smad signaling pathways, including the PI3K-Akt-mTOR pathway, Erk MAPK and p38 MAPK signaling, and Rho GTPases65,89 (Figure 2D). These pathways, however, are not diagnostic of TGF-β signaling, since they are strongly activated by receptor tyrosine kinases90.”

    From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [90]

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Cited by

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Authors
Lemmon, M. A., & Schlessinger, J.
Affiliations
  • University of Pennsylvania (US)
  • Yale University (US)
Corresponding author
  • Lemmon, Mark A.
  • Schlessinger, Joseph
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2010-06
Volume
141
Issue
7
Pages
1117-1134
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2010.06.011
PMC
PMC2914105
OpenAlex
W2028415754
Cited by
7,929
References
14
Citations by year
2026: 253 · 2025: 286 · 2024: 367 · 2023: 385 · 2022: 404 · 2021: 492 · 2020: 408 · 2019: 430 · 2018: 370 · 2017: 381 · 2016: 385 · 2015: 409 · 2014: 394 · 2013: 368 · 2012: 368
FWCI
45.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R01CA079992, R01CA096768, R01CA125432)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR051448, P50AR054086, R01AR051886)
Topics
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
receptor tyrosine kinase, ligand-induced dimerization, growth factor signaling, cancer
MeSH terms
Animals, Enzyme Activation, Humans, Neoplasms, Signal Transduction, Receptor Protein-Tyrosine Kinases

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