G Protein-Coupled Receptors Go Extracellular: RhoA Integrates the Integrins

Walsh, C. T.; Stupack, D.; Brown, J. H.

doi:10.1124/mi.8.4.8

Cited by 40Protein Kinase Regulation and GTPase SignalingReceptor Mechanisms and SignalingConnective Tissue Growth Factor Research

G Protein-Coupled Receptors Go Extracellular: RhoA Integrates the Integrins

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Walsh, C. T., Stupack, D., Brown, J. H.·2008·Molecular Interventions

DOI 10.1124/mi.8.4.8PMC PMC2637220

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Abstract

The identification of downstream effectors of G protein-coupled receptors (GPCRs) is critical for understanding the interactions between signaling cascades and for developing new pharmacological approaches for controlling GPCR-mediated responses. RhoA is a small G protein that serves as a proximal downstream effector of numerous GPCRs and regulates a variety of basic cell functions, including migration, survival, and proliferation. Intriguingly, GPCR ligands such as thrombin, sphingosine-1-phosphate, and lysophosphatidic acid, which signal through G(12/13) and activate RhoA, have recently been shown to induce the expression of the extracellular matrix protein Cyr61 (i.e., CCN1). Cyr61 is secreted and interacts with cell surface integrins to activate kinase and transcriptional cascades that are also known to contribute to cell migration, survival, and proliferation. The GPCR/RhoA/Cyr61/integrin pathway defines a novel convergence mechanism for integrating GPCR-and integrin-dependent signaling cascades that may contribute to sustained and pathophysiological responses to GPCR activation.

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Thrombin acts through GPCR and RhoA signaling to induce CCN1, which then interacts with integrins to promote cell proliferation, connecting GPCR and integrin signaling to enhance thrombin-induced cell proliferation.
“Thrombin acts through the GPCR and RhoA signaling pathways to induce CCN1, which in turn interacts with integrins to promote cell proliferation [35]. Thus, CCN1 serves to connect the GPCR and integrin signaling pathways to enhance thrombin-induced cell proliferation [38].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [38]

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Retracted
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Authors: Walsh, C. T., Stupack, D., & Brown, J. H.
Affiliations: University of California San Diego (US)
ORCID: Stupack, D.
Brown, J. H.
Venue: Molecular Interventions
Publisher: CLOCKSS Archive
Published: 2008-08-01
Volume: 8
Issue: 4
Pages: 165-173
ISSN: 1534-0384 (ISSN-L)
DOI: 10.1124/mi.8.4.8
PMC: PMC2637220
OpenAlex: W2077835424
Cited by: 40
References: 70
Citations by year: 2026: 1 · 2025: 1 · 2024: 4 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 3 · 2012: 4
FWCI: 1.37
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
Locations: Molecular Interventions (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA218859)
National Institute of General Medical Sciences (R56GM036927, R01GM036927)
Topics: 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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
Keywords: G protein-coupled receptors, RhoA, CYR61, integrins, thrombin, sphingosine-1-phosphate, lysophosphatidic acid, extracellular matrix, cell migration, cell survival, cell proliferation
MeSH terms: Animals, Extracellular Space, Humans, Signal Transduction, Integrins, rhoA GTP-Binding Protein, Intercellular Signaling Peptides and Proteins, Receptors, G-Protein-Coupled

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G Protein-Coupled Receptors Go Extracellular: RhoA Integrates the Integrins

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