GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization
Sci Signal. 2024 Feb 13;17(823):eadd9139. doi: 10.1126/scisignal.add9139. Epub 2024 Feb 13.ABSTRACTSome G protein-coupled receptors (GPCRs) demonstrate biased signaling such that ligands of the same receptor exclusively or preferentially activate certain downstream signaling pathways over others. This phenomenon may result from ligand-specific receptor phosphorylation by GPCR kinases (GRKs). GPCR signaling can also exhibit location bias because GPCRs traffic to and signal from subcellular compartments in addition to the plasma membrane. Here, we investigated whether GRKs contributed to location bias in GPCR signaling. GRKs...
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Julia Gardner Dylan Scott Eiger Chloe Hicks Issac Choi Uyen Pham Anand Chundi Ojas Namjoshi Sudarshan Rajagopal Source Type: research
RNAs create a sticky situation
Sci Signal. 2024 Feb 13;17(823):eado4078. doi: 10.1126/scisignal.ado4078. Epub 2024 Feb 13.ABSTRACTGlycated RNAs on neutrophils enable adhesion to the endothelium and extravasation to sites of inflammation.PMID:38349967 | DOI:10.1126/scisignal.ado4078 (Source: Science Signaling)
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Wei Wong Source Type: research
Mechanisms of biased agonism by G α < sub > i/o < /sub > -biased stapled peptide agonists of the relaxin-3 receptor
Sci Signal. 2024 Feb 13;17(823):eabl5880. doi: 10.1126/scisignal.abl5880. Epub 2024 Feb 13.ABSTRACTThe neuropeptide relaxin-3 is composed of an A chain and a B chain held together by disulfide bonds, and it modulates functions such as anxiety and food intake by binding to and activating its cognate receptor RXFP3, mainly through the B chain. Biased ligands of RXFP3 would help to determine the molecular mechanisms underlying the activation of G proteins and β-arrestins downstream of RXFP3 that lead to such diverse functions. We showed that the i, i+4 stapled relaxin-3 B chains, 14s18 and d(1-7)14s18, were Gαi/o-biased ago...
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Tharindunee Jayakody Asuka Inoue Srinivasaraghavan Kannan Gaku Nakamura Kouki Kawakami Krishan Mendis Thanh-Binh Nguyen Jianguo Li Deron R Herr Chandra S Verma Gavin S Dawe Source Type: research
GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization
Sci Signal. 2024 Feb 13;17(823):eadd9139. doi: 10.1126/scisignal.add9139. Epub 2024 Feb 13.ABSTRACTSome G protein-coupled receptors (GPCRs) demonstrate biased signaling such that ligands of the same receptor exclusively or preferentially activate certain downstream signaling pathways over others. This phenomenon may result from ligand-specific receptor phosphorylation by GPCR kinases (GRKs). GPCR signaling can also exhibit location bias because GPCRs traffic to and signal from subcellular compartments in addition to the plasma membrane. Here, we investigated whether GRKs contributed to location bias in GPCR signaling. GRKs...
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Julia Gardner Dylan Scott Eiger Chloe Hicks Issac Choi Uyen Pham Anand Chundi Ojas Namjoshi Sudarshan Rajagopal Source Type: research
RNAs create a sticky situation
Sci Signal. 2024 Feb 13;17(823):eado4078. doi: 10.1126/scisignal.ado4078. Epub 2024 Feb 13.ABSTRACTGlycated RNAs on neutrophils enable adhesion to the endothelium and extravasation to sites of inflammation.PMID:38349967 | DOI:10.1126/scisignal.ado4078 (Source: Science Signaling)
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Wei Wong Source Type: research
Mechanisms of biased agonism by G α < sub > i/o < /sub > -biased stapled peptide agonists of the relaxin-3 receptor
Sci Signal. 2024 Feb 13;17(823):eabl5880. doi: 10.1126/scisignal.abl5880. Epub 2024 Feb 13.ABSTRACTThe neuropeptide relaxin-3 is composed of an A chain and a B chain held together by disulfide bonds, and it modulates functions such as anxiety and food intake by binding to and activating its cognate receptor RXFP3, mainly through the B chain. Biased ligands of RXFP3 would help to determine the molecular mechanisms underlying the activation of G proteins and β-arrestins downstream of RXFP3 that lead to such diverse functions. We showed that the i, i+4 stapled relaxin-3 B chains, 14s18 and d(1-7)14s18, were Gαi/o-biased ago...
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Tharindunee Jayakody Asuka Inoue Srinivasaraghavan Kannan Gaku Nakamura Kouki Kawakami Krishan Mendis Thanh-Binh Nguyen Jianguo Li Deron R Herr Chandra S Verma Gavin S Dawe Source Type: research
GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization
Sci Signal. 2024 Feb 13;17(823):eadd9139. doi: 10.1126/scisignal.add9139. Epub 2024 Feb 13.ABSTRACTSome G protein-coupled receptors (GPCRs) demonstrate biased signaling such that ligands of the same receptor exclusively or preferentially activate certain downstream signaling pathways over others. This phenomenon may result from ligand-specific receptor phosphorylation by GPCR kinases (GRKs). GPCR signaling can also exhibit location bias because GPCRs traffic to and signal from subcellular compartments in addition to the plasma membrane. Here, we investigated whether GRKs contributed to location bias in GPCR signaling. GRKs...
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Julia Gardner Dylan Scott Eiger Chloe Hicks Issac Choi Uyen Pham Anand Chundi Ojas Namjoshi Sudarshan Rajagopal Source Type: research
RNAs create a sticky situation
Sci Signal. 2024 Feb 13;17(823):eado4078. doi: 10.1126/scisignal.ado4078. Epub 2024 Feb 13.ABSTRACTGlycated RNAs on neutrophils enable adhesion to the endothelium and extravasation to sites of inflammation.PMID:38349967 | DOI:10.1126/scisignal.ado4078 (Source: Science Signaling)
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Wei Wong Source Type: research
Mechanisms of biased agonism by G α < sub > i/o < /sub > -biased stapled peptide agonists of the relaxin-3 receptor
Sci Signal. 2024 Feb 13;17(823):eabl5880. doi: 10.1126/scisignal.abl5880. Epub 2024 Feb 13.ABSTRACTThe neuropeptide relaxin-3 is composed of an A chain and a B chain held together by disulfide bonds, and it modulates functions such as anxiety and food intake by binding to and activating its cognate receptor RXFP3, mainly through the B chain. Biased ligands of RXFP3 would help to determine the molecular mechanisms underlying the activation of G proteins and β-arrestins downstream of RXFP3 that lead to such diverse functions. We showed that the i, i+4 stapled relaxin-3 B chains, 14s18 and d(1-7)14s18, were Gαi/o-biased ago...
Source: Science Signaling - February 13, 2024 Category: Biomedical Science Authors: Tharindunee Jayakody Asuka Inoue Srinivasaraghavan Kannan Gaku Nakamura Kouki Kawakami Krishan Mendis Thanh-Binh Nguyen Jianguo Li Deron R Herr Chandra S Verma Gavin S Dawe Source Type: research
Cbl-b mitigates the responsiveness of naive CD8 < sup > + < /sup > T cells that experience extensive tonic T cell receptor signaling
Sci Signal. 2024 Feb 6;17(822):eadh0439. doi: 10.1126/scisignal.adh0439. Epub 2024 Feb 6.ABSTRACTNaive T cells experience tonic T cell receptor (TCR) signaling in response to self-antigens presented by major histocompatibility complex (MHC) in secondary lymphoid organs. We investigated how relatively weak or strong tonic TCR signals influence naive CD8+ T cell responses to stimulation with foreign antigens. The heterogeneous expression of Nur77-GFP, a transgenic reporter of tonic TCR signaling, in naive CD8+ T cells suggests variable intensities or durations of tonic TCR signaling. Although the expression of genes associat...
Source: Science Signaling - February 6, 2024 Category: Biomedical Science Authors: Joel Eggert Wendy M Zinzow-Kramer Yuesong Hu Elizabeth M Kolawole Yuan-Li Tsai Arthur Weiss Brian D Evavold Khalid Salaita Christopher D Scharer Byron B Au-Yeung Source Type: research
Extracellular WNT conveyors
Sci Signal. 2024 Feb 6;17(822):eado3060. doi: 10.1126/scisignal.ado3060. Epub 2024 Feb 6.ABSTRACTThe extracellular WNT-binding proteins SFRP and WIF1 promote and inhibit WNT signaling.PMID:38319999 | DOI:10.1126/scisignal.ado3060 (Source: Science Signaling)
Source: Science Signaling - February 6, 2024 Category: Biomedical Science Authors: Annalisa M VanHook Source Type: research
A mammalian-specific Alex3/G α < sub > q < /sub > protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival
Sci Signal. 2024 Feb 6;17(822):eabq1007. doi: 10.1126/scisignal.abq1007. Epub 2024 Feb 6.ABSTRACTMitochondrial dynamics and trafficking are essential to provide the energy required for neurotransmission and neural activity. We investigated how G protein-coupled receptors (GPCRs) and G proteins control mitochondrial dynamics and trafficking. The activation of Gαq inhibited mitochondrial trafficking in neurons through a mechanism that was independent of the canonical downstream PLCβ pathway. Mitoproteome analysis revealed that Gαq interacted with the Eutherian-specific mitochondrial protein armadillo repeat-containing X-l...
Source: Science Signaling - February 6, 2024 Category: Biomedical Science Authors: Ismael Izquierdo-Villalba Serena Mirra Yasmina Manso Antoni Parcerisas Javier Rubio Jaume Del Valle Francisco J Gil-Bea Fausto Ulloa Marina Herrero-Lorenzo Ester Verdaguer Cristiane Beninc á Rub én D Castro-Torres Elena Rebollo Gemma Marfany Carme Aulad Source Type: research
Free cGAS
Sci Signal. 2024 Jan 30;17(821):eado2601. doi: 10.1126/scisignal.ado2601. Epub 2024 Jan 30.ABSTRACTThe DNA double-strand break sensor MRE11 is necessary to liberate cGAS and enable its activation by dsDNA.PMID:38289984 | DOI:10.1126/scisignal.ado2601 (Source: Science Signaling)
Source: Science Signaling - January 30, 2024 Category: Biomedical Science Authors: Amy E Baek Source Type: research
Pannexin-3 stabilizes the transcription factor Bcl6 in a channel-independent manner to protect against vascular oxidative stress
Sci Signal. 2024 Jan 30;17(821):eadg2622. doi: 10.1126/scisignal.adg2622. Epub 2024 Jan 30.ABSTRACTTargeted degradation regulates the activity of the transcriptional repressor Bcl6 and its ability to suppress oxidative stress and inflammation. Here, we report that abundance of endothelial Bcl6 is determined by its interaction with Golgi-localized pannexin 3 (Panx3) and that Bcl6 transcriptional activity protects against vascular oxidative stress. Consistent with data from obese, hypertensive humans, mice with an endothelial cell-specific deficiency in Panx3 had spontaneous systemic hypertension without obvious changes in c...
Source: Science Signaling - January 30, 2024 Category: Biomedical Science Authors: Abigail G Wolpe Melissa A Luse Christopher Baryiames Wyatt J Schug Jacob B Wolpe Scott R Johnstone Luke S Dunaway Zuzanna J Ju śkiewicz Skylar A Loeb Henry R Askew Page Yen-Lin Chen Vikram Sabapathy Caitlin M Pavelec Brent Wakefield Eugenia Cifuentes-Pag Source Type: research
A plasma membrane-associated form of the androgen receptor enhances nuclear androgen signaling in osteoblasts and prostate cancer cells
Sci Signal. 2024 Jan 30;17(821):eadi7861. doi: 10.1126/scisignal.adi7861. Epub 2024 Jan 30.ABSTRACTAndrogen binding to the androgen receptor (AR) in the cytoplasm induces the AR to translocate to the nucleus, where it regulates the expression of target genes. Here, we found that androgens rapidly activated a plasma membrane-associated signaling node that enhanced nuclear AR functions. In murine primary osteoblasts, dihydrotestosterone (DHT) binding to a membrane-associated form of AR stimulated plasma membrane-associated protein kinase G type 2 (PKG2), leading to the activation of multiple kinases, including ERK. Phosphory...
Source: Science Signaling - January 30, 2024 Category: Biomedical Science Authors: Hema Kalyanaraman Darren E Casteel Shyamsundar Pal China Shunhui Zhuang Gerry R Boss Renate B Pilz Source Type: research
