October 2022 Regulation of pulmonary surfactant by the adhesion GPCR GPR116/ADGRF5 requires a tethered agonist-mediated activation mechanism "The mechanistic details of the tethered agonist mode of activation for the adhesion GPCR ADGRF5/GPR116 have not been completely deciphered. We set out to investigate the physiological importance of autocatalytic cleavage upstream of the agonistic peptide sequence, an event necessary for NTF displacement and subsequent receptor activation. To examine this hypothesis, we characterized tethered agonist-mediated activation of GPR116 in vitro and in vivo. A knock-in mouse expressing a non-cleavable GPR116 mutant phenocopies the pulmonary phenotype of GPR116 knock-out mice, demonstrating that tethered agonist-mediated receptor activation is indispensable for function in vivo. Using site-directed mutagenesis and species-swapping approaches, we identified key conserved amino acids for GPR116 activation in the tethered agonist sequence and in extracellular loops 2/3 (ECL2/3). We further highlight residues in transmembrane 7 (TM7) that mediate stronger signaling in mouse versus human GPR116 and recapitulate these findings in a model supporting tethered agonist:ECL2 interactions for GPR116 activation." Read more at the source #DrGPCR #GPCR #IndustryNews

the efficacy of seven agonists to induce G protein, G protein-coupled receptor kinase 2 (GRK2), as well

October 2022 Use of CRISPR/Cas9-edited HEK293 cells reveals that both conventional and novel protein In this study, we generated and characterized human embryonic kidney 293A (HEK293A) cell lines devoid Additionally, using the Gαq/11 inhibitor YM-254890, GPCR kinase 2 and 3 (GRK2 and GRK3) KO cells, and Our PKC KO cell lines expand the repertoire of KO HEK293A cell lines available to research GPCR pharmacology lines as more specific research tools to investigate PKC-mediated aspects of cell biology."

of Technology in Genova, Italy (2008-2016) and an Associate Research Professor in the Department of Cell Biology at Duke University in North Carolina, USA (1996-2008). Before joining the Department of Cell Biology in 1996 as a postdoc and becoming faculty at Duke in 2000 As of August 2022, he has over 270 publications in scientific journals (including Science, Nature, Cell

Cardarelli is a drug development leader with extensive experience driving drug discovery teams in bringing biologics She has expertise in cell biology, pharmacology, translational medicine, oncology, immuno-oncology, immunology Previously, she held the position of Vice President of Cell Biology & Pharmacology, at Bristol-Myers She has extensive experience working with Biologics, and Antibody Drug Conjugates as well as experience

Eldridge Distinguished Professor and Chair of the Department of Cell Biology & Physiology at The University Caron received a BS in Biology and BA in Philosophy at Emory University and a PhD at Duke University special emphasis on G protein coupled receptors and receptor activity modifying proteins in vascular biology Kathleen Caron on the web UNC-Chapel Hill Department of Cell Biology and Physiology UNC Lineberger Comprehensive