Chasing Down a Cellular “Short Circuit”

Team of researchers at UC San Diego identifies cause of cellular miscommunication implicated in the origin of many human diseases

ONLINE COVER This week, Roy et al. show that cross-talk between the growth factor receptor EGFR and the chemokine receptor CXCR4 occurs at the level of phosphorylation of the G protein α-subunit, Gαi. The image shows a three-dimensional structure of Gαi, with the identified phosphorylation sites shown in blue. (Image: Roy et al./Science Signaling).
A group of researchers at the University of California San Diego has identified the cause of a “short-circuit” in cellular pathways, a discovery that sheds new light on the genesis of a number of human diseases. The recent study, published June 4, 2024 in the journal Science Signaling, (and serving as the cover story of that issue) explores the biochemical mechanism that can interrupt the cellular communication chain — a disruptive interaction that Pradipta Ghosh, MD, likens to a game-ending “buzzer.” Ghosh, a Professor in the Departments of Medicine and Cellular and Molecular Medicine at University of California San Diego School of Medicine, and Irina Kufareva, Ph.D., an Associate Professor in the Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego, are the corresponding authors on the paper. The paper is titled “Growth Factor–Dependent Phosphorylation of Gαi Shapes Canonical Signaling by G Protein–Coupled Receptors.”
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