Integrin-mediated signalling through the MAP-kinase pathway

Yee, K.L.; Weaver, V.M.; Hammer, D.A.

doi:10.1049/iet-syb:20060058

Cited by 117Protein Kinase Regulation and GTPase SignalingCell Adhesion Molecules ResearchGene Regulatory Network Analysis

Integrin-mediated signalling through the MAP-kinase pathway

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Yee, K.L., Weaver, V.M., Hammer, D.A.·2008·IET Systems Biology

DOI 10.1049/iet-syb:20060058

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Abstract

The mitogen activated protein (MAP) kinase cascade, leading to extracellular-regulated kinase (ERK) activation, is a key regulator of cell growth and proliferation. The effects of ERK are mediated by differences in ERK signalling dynamics, including magnitude and duration. In vivo, ERK signalling is stimulated by both growth factors and adhesion signals. A model for adhesion-mediated ERK activation is presented. Outputs of the model such as ERK and FAK activation, as well as responses to different ligand densities, are compared with published experimental data. The model then serves as a basis for understanding how adhesion may contribute to ERK signalling through changes in the dynamics of focal adhesion kinase activation. The main parameters influencing ERK are determined through screening analyses and parameter variation. With these parameters, key points in the pathway that give rise to changes in downstream signalling dynamics are identified. In particular, oncogenic Raf and Ras promote cell growth by increasing the magnitude and duration, respectively, of ERK activity.

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The MAPK/ERK cascade is a key regulator of cell growth and proliferation, and this signaling pathway activates the binding of different integrins at the cell surface to extracellular matrix proteins.
“The MAPK/ERK cascade is a key regulator of cell growth and proliferation, but most important, this signaling pathway activates the binding of different integrins at the cell surface to extracellular matrix proteins [60], linking its function with the up-regulated integrin pathway explained above.”
From Gene expression profiles underlying aggressive behavior in the prefrontal cortex of cattle (2021) · cites this paper as [60]

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Authors: Yee, K. L., Weaver, V. M., & Hammer, D. A.
Affiliations: University of Pennsylvania (US)
University of California, San Francisco (US)
ORCID: Yee, K.L.
Weaver, V.M.
Venue: IET Systems Biology
Publisher: Institution of Engineering and Technology (IET)
Published: 2008-01-21
Volume: 2
Issue: 1
Pages: 8-15
ISSN: 1751-8849 (ISSN-L)
1751-8857
DOI: 10.1049/iet-syb:20060058
OpenAlex: W2023251706
Cited by: 117
References: 51
Citations by year: 2026: 6 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 9 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 3 · 2016: 6 · 2015: 6 · 2014: 11 · 2013: 4 · 2012: 6
FWCI: 0.82
Type: journal article
Language: en
Open access: green
repository.upenn.edu
Locations: IET Systems Biology (publishedVersion)
PubMed (publishedVersion)
ScholarlyCommons (University of Pennsylvania) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords: integrin signaling, MAP kinase cascade, ERK activation, focal adhesion kinase, ligand density, oncogenic Ras, cell growth and proliferation
MeSH terms: Animals, Humans, Models, Biological, Integrins, ras Proteins, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System

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Integrin-mediated signalling through the MAP-kinase pathway

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