Scientists at the University of California San Diego (UCSD) School of Medicine say they have unraveled new insights into the way cells leverage GPCRs and their cellular waste disposal systems to control inflammation. Their study (“ A Tyrosine Switch on NEDD4-2 E3 Ligase Transmits GPCR Inflammatory Signaling ”), published in Cell Reports , suggests some existing cancer drugs that inhibit these cellular activities might be repurposed to treat vascular inflammation, which occurs when artery-blocking plaques form in atherosclerosis. “Ubiquitination is essential for protein degradation and signaling and pivotal to many physiological processes. Ubiquitination of a subset of G-protein-coupled receptors (GPCRs) by the E3 ligase NEDD4-2 is required for p38 activation, but how GPCRs activate NEDD4-2 to promote ubiquitin-mediated signaling is not known. Here, we report that the GPCR protease-activated receptor-1 (PAR1) stimulates c-Src-mediated tyrosine phosphorylation and activation of NEDD4-2 to promote p38 signaling and endothelial barrier disruption,” write ...
Original Article: Some Cancer Drugs Might Be Repurposed to Treat Vascular Inflammation