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Updated: Apr 18, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
GIV/Girdin transmits signals from multiple receptors by triggering trimeric G protein activation
Mikel Garcia-Marcos1, Pradipta Ghosh2, Marilyn G Farquhar3
1From the Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118 and mgm1@bu.edu.
Abstract:
Activation of trimeric G proteins has been traditionally viewed as the exclusive job of G protein-coupled receptors (GPCRs). This view has been challenged by the discovery of non-receptor activators of trimeric G proteins. Among them, GIV (a.k.a. Girdin) is the first for which a guanine nucleotide exchange factor (GEF) activity has been unequivocally associated with a well defined motif. Here we discuss how GIV assembles alternative signaling pathways by sensing cues from various classes of surface receptors and relaying them via G protein activation. We also describe the dysregulation of this mechanism in disease and how its targeting holds promise for novel therapeutics.
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