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Updated: Jul 14, 2026
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
GPCRs signaling directly through Src-family kinases
Deirdre McGarrigle1, Xin-Yun Huang
1Department of Physiology, Cornell University Weill Medical College, New York, NY 10021, USA.
Summary
G protein-coupled receptors (GPCRs) can activate G proteins or signal independently. Agonist dosage may control whether GPCRs use G protein-dependent or G protein-independent pathways, including interaction with Src-family kinases.
Area of Science:
- Cellular signaling
- Molecular biology
- Biochemistry
Background:
- G protein-coupled receptors (GPCRs) are key mediators of cellular responses to extracellular signals.
- GPCR activation typically involves heterotrimeric guanine nucleotide-binding proteins (G proteins) that regulate downstream effectors.
- Emerging evidence suggests alternative signaling pathways for GPCRs independent of G proteins.
Purpose of the Study:
- To review the evidence for direct interaction between GPCRs and Src-family kinases (SFKs).
- To explore the role of agonist dosage in modulating GPCR signaling pathways.
- To elucidate the mechanism by which GPCRs switch between G protein-dependent and G protein-independent signaling.
Main Methods:
- Literature review of studies investigating GPCR-SFK interactions.
- Analysis of data on GPCR activation and downstream signaling.
- Examination of the impact of varying agonist concentrations on signaling outcomes.
Main Results:
- Several GPCRs have been shown to directly interact with and activate SFKs.
- Agonist dosage emerges as a critical factor influencing GPCR signaling mode.
- GPCRs can transition between G protein-dependent and G protein-independent signaling pathways.
Conclusions:
- GPCRs possess dual signaling capabilities, engaging both G protein-dependent and G protein-independent pathways.
- The interaction with SFKs represents a significant G protein-independent signaling mechanism for GPCRs.
- Agonist concentration is a key determinant in directing GPCRs toward specific signaling cascades, offering a novel regulatory mechanism.
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