October 2022 "Systolic heart failure (HF) is a chronic clinical syndrome characterized by the reduction in cardiac function and still remains the disease with the highest mortality worldwide. Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social burden. Chronic human HF is characterized by several important neurohormonal perturbations, emanating from both the autonomic nervous system and the adrenal glands. Circulating catecholamines (norepinephrine and epinephrine) and aldosterone elevations are among the salient alterations that confer significant hormonal burden on the already compromised function of the failing heart. This is why sympatholytic treatments (such as β-blockers) and renin-angiotensin system inhibitors or mineralocorticoid receptor antagonists, which block the effects of angiotensin II (AngII) and aldosterone on the failing heart, are part of the mainstay HF pharmacotherapy presently. The adrenal gland plays an important role in the modulation of cardiac neurohormonal stress because it is the source of almost all aldosterone, of all epinephrine, and of a significant amount of norepinephrine reaching the failing myocardium from the blood circulation. Synthesis and release of these hormones in the adrenals is tightly regulated by adrenal G protein-coupled receptors (GPCRs), such as adrenergic receptors and AngII receptors. In this review, we discuss important aspects of adrenal GPCR signaling and regulation, as they pertain to modulation of cardiac function in the context of chronic HF, by focusing on the 2 best studied adrenal GPCR types in that context, adrenergic receptors and AngII receptors (AT 1 Rs). Particular emphasis is given to findings from the past decade and a half that highlight the emerging roles of the GPCR-kinases and the β-arrestins in the adrenals, 2 protein families that regulate the signaling and functioning of GPCRs in all tissues, including the myocardium and the adrenal gland." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Regulator of G Protein Signaling 20 Correlates with Long Intergenic Non-Coding RNA (lincRNAs ; (d) RGS20 was found to be significantly associated with some tumor-related signaling pathways and long

October 2022 β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling advanced NanoLuc/FlAsH-based biosensors reveals distinct conformational signatures of β-arrestin1 and 2 when

this has the potential to enhance GPCR subtype-selectivity, it also presents a significant challenge when modulators (NAMs), that fully or partially dampen the receptor's functional response to the ligand (Wold, Chen and NAMs and thereby blocks the effects of positive and negative allosteric modulators (Rodriguez, Nong This is particularly important when dealing with receptor subtypes that exhibit significant similarity substantial doses of allosteric modulators with a diminished risk of target-related toxicity (Wold, Chen

and subsequent activation of the G-protein heterotrimeric complex (α, β, and γ); it is at this point when Liu-Chen, and J.R. J Biol Chem, 2009. 284(27): p. 18357-67. https://pubmed.ncbi.nlm.nih.gov/19416973/ 5.

Through developing a high-resolution method, Hao Chen et al. directly visualized the fusion of vesicles Chen, X. Zhang, and L. Ma. 2008.

activation initiates conformational changes, exposing an intracellular cavity (Kang, Y. et al. 2015, Chen recognized for inhibiting G protein signaling, they also influence specific pathways such as MAPK signaling (Song F et al. 2021, Chen, H. et al. 2022). , as well as MAPK cascade kinases which can be activated through specific β-arrestin conformations (Song

J Biol Chem, 2018. 293(19): p. 7466-7473. 8.      Nat Chem Biol, 2020. 16(8): p. 841-849. 10.    J Biol Chem, 2007. 282(14): p. 10576-84. 13.   

Structurally they characterize by a long extracellular region of adhesion-like domains which modulate When I started studying aGPCRs, the structural conformation of the GAIN domain of ADGRL1/Lphn1 and ADGRB3 of human ADGRL3-G13, this paper reports that the stalk peptide of ADGRL3 adopts a hook conformation when Furthermore, when an alignment analysis of the Stalk peptide of the aGPCR family was performed highlighted ., Zhu, X., Wang, N., Xu, Z., Xia, R., Liang, J., Duan, Y., Yin, H., Xiong, Y., Zhang, A., Guo, C., Chen

When it comes to signal transduction, cellular context matters. Pharmaceuticals (Basel, Switzerland), 14(5), 439. https://doi.org/10.3390/ph14050439 Chen, K. Nature communications, 8(1), 443. https://doi.org/10.1038/s41467-017-00357-2 Jong, Y.

., Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes Chem Rev, 2017. 117 (1): p. 111-138.

Norton Cheng and Dr.

Dysfunction of the adhesion GPCR latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity Norton Cheng

When comparing the CKRs structures complexes, the disulfide bridges formed between the N-loop and the interaction follows a common pattern which is generally described by the classic “two-site” model (Crump, Gong agonist (maraviroc) (Tan, Zhu et al. 2013, Zheng, Han et al. 2017, Isaikina, Tsai et al. 2021, Zhang, Chen CCL15L (residues 26-92) and CCL15M (residues 27-92), while the third structure lacks a ligand (Shao, Shen conformational change of Y2917.43 tilted toward TM2, a model supported by mutagenesis experiments (Shao, Shen

Experienced Pharmaceutical Executive Toshihiro Maeda as Chief Operating Officer Rhythm Pharmaceuticals and LG Chem

Artificial intelligence - Machine learning vs Deep Learning GPCRs have long been recognized as important predict subtype-selective ligands for dopamine receptors and adenosine receptors (He, Ben, Kuang, Wang & Kong , 2016; Kuang, Feng, Hu, Wang, He & Kong, 2016). 5. ability of a ligand to induce or inhibit a cellular response (pEC50 or pIC50, respectively), and how long similarity cannot adequately predict protein structure (Jumper et al., 2021) ); 3) the same limitation holds when

Our results reveal that the extended N-terminus of the long isoform limits G protein activation yet elevates constitutive G13 activation, while an additional cysteine contributed by the extended N-terminus of the long

GPCRs have been long considered as controllers of communication between tissues and cells. receptorsomes, both at the cell surface membrane and in the intracellular domain dictate and condition long-term

Here, we investigate the effects that long-term CNO stimulatory culture have on hM3Dq [Ca2+]i signaling Long-term culturing under repeated CNO stimulation modified the temporal dynamics of hM3Dq [Ca2+]i signaling

adopted to elucidate the structure, pharmacology, and signaling of cardiovascular GPCRs, resolving long-standing

Sir William Osler Scientists have long sought to discover a “golden bullet” that would cure every disease signal-regulated kinases (ERK), a subset of the mitogen-activated protein kinase (MAPK) family, have long The gravity of this regulation becomes even more apparent when we consider the potential consequences

disease before they can even dare to contemplate the development of therapeutic options and begin the long

We show that besides classical hydrogen bonds, weak polar interactions such as O-HC, O-Br, and long-range

heterogeneous disease with few effective targeted therapies and precision therapeutic options over a long

The excitement I felt when I first attended back in Boston is the same one I feel now that I am the organizer When in Mexico City from 23-25 October, here is my bucket list of the 3 things that people should absolutely What mariachi song are you most likely to shout along to at 3 AM? Mariachi song: I typically do not sing to these since they are dear to Mexican childhood memories, and

Adrenomedullin 2/intermedin is a slow off-rate, long-acting endogenous agonist of the adrenomedullin2

pyrimidines as Tools to Investigate A3 Adenosine Receptors in Cancer Cell Lines Severity of neurological long-COVID

Research CPGL: Prediction of Compound-Protein Interaction by Integrating Graph Attention Network With Long