Ubiquitin-driven G Protein-Coupled Receptor Inflammatory Signaling at the Endosome

Am J Physiol Cell Physiol. 2024 Apr 22. doi: 10.1152/ajpcell.00161.2024. Online ahead of print.ABSTRACTG protein-coupled receptors (GPCRs) are ubiquitously expressed cell surface receptors that mediate numerous physiological responses and are highly druggable. Upon activation GPCRs rapidly couple to heterotrimeric G proteins and are then phosphorylated and internalized from the cell surface. Recent studies indicate that GPCRs not only localize at the plasma membrane but also exist in intracellular compartments where they are competent to signal. Intracellular signaling by GPCRs is best described to occur at endosomes. Several studies have elegantly documented endosomal GPCR-G protein and GPCR-β-arrestin signaling. Besides phosphorylation, GPCRs are also post-translationally modified with ubiquitin. GPCR ubiquitination has been studied mainly in the context of receptor endosomal-lysosomal trafficking. However, new studies indicate that ubiquitination of endogenous GPCRs expressed in endothelial cells initiates the assembly of an intracellular p38 mitogen-activated kinase signaling complex that promotes inflammatory responses. In this mini-review, we discuss emerging discoveries that provide critical insight into the function of ubiquitination in regulating GPCR inflammatory signaling at endosomes.PMID:38646783 | DOI:10.1152/ajpcell.00161.2024

Source: Am J Physiol Cell Ph... - April 22, 2024 Category: Cytology Authors: Norton Cheng Julio M Pimentel JoAnn Trejo Source Type: research