Functional diversification of cell signaling by GPCR localization

MJ Klauer, BKA Willette, NG Tsvetanova - Journal of Biological Chemistry, 2024 - jbc.org
G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and a
critical class of regulators of mammalian physiology. Also known as seven transmembrane …

Know your molecule: pharmacological characterization of drug candidates to enhance efficacy and reduce late-stage attrition

T Kenakin - Nature Reviews Drug Discovery, 2024 - nature.com
Despite advances in chemical, computational and biological sciences, the rate of attrition of
drug candidates in clinical development is still high. A key point in the small-molecule …

GLP-1R signaling neighborhoods associate with the susceptibility to adverse drug reactions of incretin mimetics

SC Wright, A Motso, S Koutsilieri, CM Beusch… - Nature …, 2023 - nature.com
G protein-coupled receptors are important drug targets that engage and activate signaling
transducers in multiple cellular compartments. Delineating therapeutic signaling from …

Structural insights into the activation and inhibition of CXC chemokine receptor 3

H Jiao, B Pang, A Liu, Q Chen, Q Pan… - Nature Structural & …, 2024 - nature.com
The chemotaxis of CD4+ type 1 helper cells and CD8+ cytotoxic lymphocytes, guided by
interferon-inducible CXC chemokine 9–11 (CXCL9–11) and CXC chemokine receptor 3 …

[HTML][HTML] CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer

RJ Lim, R Salehi-Rad, LM Tran, MS Oh, C Dumitras… - Cell Reports …, 2024 - cell.com
Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the
treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are …

G protein–coupled receptor endocytosis generates spatiotemporal bias in β-arrestin signaling

AD Tóth, B Szalai, OT Kovács, D Garger, S Prokop… - Science …, 2024 - science.org
The stabilization of different active conformations of G protein–coupled receptors is thought
to underlie the varying efficacies of biased and balanced agonists. Here, profiling the …

Phosphorylation barcodes direct biased chemokine signaling at CXCR3

DS Eiger, JS Smith, T Shi, TM Stepniewski, CF Tsai… - Cell chemical …, 2023 - cell.com
G protein-coupled receptor (GPCR)-biased agonism, selective activation of certain signaling
pathways relative to others, is thought to be directed by differential GPCR phosphorylation" …

GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization

J Gardner, DS Eiger, C Hicks, I Choi, U Pham… - Science …, 2024 - science.org
Some G protein–coupled receptors (GPCRs) demonstrate biased signaling such that
ligands of the same receptor exclusively or preferentially activate certain downstream …

Arrestin‐centred interactions at the membrane and their conformational determinants

O Underwood, RS Haider, J Sanchez… - British Journal of …, 2024 - Wiley Online Library
More than 30 years after their discovery, arrestins are recognised multiprotein scaffolds that
play essential roles in G protein‐coupled receptor (GPCR) regulation and signalling …

Phosphorylation patterns in the AT1R C-terminal tail specify distinct downstream signaling pathways

C Gareri, CT Pfeiffer, X Jiang, JA Paulo, SP Gygi… - Science …, 2024 - science.org
Different ligands stabilize specific conformations of the angiotensin II type 1 receptor (AT1R)
that direct distinct signaling cascades mediated by heterotrimeric G proteins or β-arrestin …