Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 275
Filtrar
1.
Cell Chem Biol ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32053779

RESUMO

G protein-coupled receptors are a major class of membrane receptors that mediate physiological and pathophysiological cellular signaling. Many aspects of receptor activation and signaling can be investigated using genetically encoded luminescent fusion proteins. However, the use of these biosensors in live cell systems requires the exogenous expression of the tagged protein of interest. To maintain the normal cellular context here we use CRISPR/Cas9-mediated homology-directed repair to insert luminescent tags into the endogenous genome. Using NanoLuc and bioluminescence resonance energy transfer we demonstrate fluorescent ligand binding at genome-edited chemokine receptors. We also demonstrate that split-NanoLuc complementation can be used to investigate conformational changes and internalization of CXCR4 and that recruitment of ß-arrestin2 to CXCR4 can be monitored when both proteins are natively expressed. These results show that genetically encoded luminescent biosensors can be used to investigate numerous aspects of receptor function at native expression levels.

2.
Br J Pharmacol ; 177(2): 346-359, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31596949

RESUMO

BACKGROUND AND PURPOSE: Adenosine is a local mediator that regulates physiological and pathological processes via activation of four GPCRs (A1 , A2A , A2B , and A3 ). We have investigated the effect of two A1 -receptor-selective agonists and the novel A1 -receptor bitopic ligand VCP746 on the rat cardiovascular system. EXPERIMENTAL APPROACH: The regional haemodynamic responses of these agonist was investigated in conscious rats. Male Sprague-Dawley rats (350-450 g) were chronically implanted with pulsed Doppler flow probes on the renal, mesenteric arteries and the descending abdominal aorta and the jugular vein and caudal artery catheterized. Cardiovascular responses were measured following intravenous infusion (3 min each dose) of CCPA (120, 400, and 1,200 ng·kg-1 ·min-1 ), capadenoson or adenosine (30, 100, and 300 µg·kg-1 ·min-1 ), or VCP746 (6, 20, and 60 µg·kg-1 ·min-1 ) following pre-dosing with DPCPX (0.1 mg·kg-1 , i.v.) or vehicle. KEY RESULTS: CCPA produced a significant A1 -receptor-mediated decrease in heart rate that was accompanied by vasoconstrictions in the renal and mesenteric vascular beds but an increase in hindquarters vascular conductance. The partial agonist capadenoson also produced an A1 -receptor-mediated bradycardia. In contrast, VCP746 produced increases in heart rate and renal and mesenteric vascular conductance that were not mediated by A1 -receptors. In vitro studies confirmed that VCP746 had potent agonist activity at both A2A - and A2B -receptors. CONCLUSIONS AND IMPLICATIONS: These results suggest VCP746 mediates its cardiovascular effects via activation of A2 rather than A1 adenosine receptors. This has implications for the design of future bitopic ligands that incorporate A1 allosteric ligand moieties.

3.
SLAS Discov ; 25(2): 186-194, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31583945

RESUMO

Receptor internalization in response to prolonged agonist treatment is an important regulator of G protein-coupled receptor (GPCR) function. The adenosine A1 receptor (A1AR) is one of the adenosine receptor family of GPCRs, and evidence for its agonist-induced internalization is equivocal. The recently developed NanoBiT technology uses split NanoLuc Luciferase to monitor changes in protein interactions. We have modified the human A1AR on the N-terminus with the small high-affinity HiBiT tag. In the presence of the large NanoLuc subunit (LgBiT), complementation occurs, reconstituting a full-length functional NanoLuc Luciferase. Here, we have used complemented luminescence to monitor the internalization of the A1AR in living HEK293 cells. Agonist treatment resulted in a robust decrease in cell-surface luminescence, indicating an increase in A1AR internalization. These responses were inhibited by the A1AR-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), with an antagonist affinity that closely matched that measured using ligand binding with a fluorescent A1 receptor antagonist (CA200645). The agonist potencies for inducing A1AR internalization were very similar to the affinities previously determined by ligand binding, suggesting little or no amplification of the internalization response. By complementing the HiBiT tag to exogenous purified LgBiT, it was also possible to perform NanoBRET ligand-binding experiments using HiBiT-A1AR. This study demonstrates the use of NanoBiT technology to monitor internalization of the A1AR and offers the potential to combine these experiments with NanoBRET ligand-binding assays.

4.
Methods Mol Biol ; 2041: 163-181, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646488

RESUMO

Fluorescent antagonists offer the ability to interrogate G protein-coupled receptor pharmacology. With resonance energy transfer techniques, fluorescent antagonists can be implemented to monitor receptor-ligand interactions using assays originally designed for radiolabeled probes. The fluorescent nature of these antagonists also enables the localization and distribution of the receptors to be visualized in living cells. Here, we describe the generation of modified purinergic receptors with the NanoLuc luciferase or SNAP-tag, using the P1 adenosine A3 receptor as an example. We also describe the procedure of characterizing a novel fluorescent purinergic antagonist using ligand-mediated bioluminescence resonance energy transfer assays and confocal microscopy.

5.
J Med Chem ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31887252

RESUMO

Among class A G protein-coupled receptors (GPCR), the human adenosine A2A receptor (hA2AAR) remains an attractive drug target. However, translation of A2AAR ligands into the clinic has proved challenging and an improved understanding of A2AAR pharmacology could promote development of more efficacious therapies. Subtype-selective fluorescent probes would allow detailed real-time pharmacological investigations both in vitro and in vivo. In the present study, two families of fluorescent probes were designed around the known hA2AAR selective antagonist preladenant (SCH 420814). Both families of fluorescent antagonists retained affinity at the hA2AAR, selectivity over all other adenosine receptor subtypes and allowed clear visualization of specific receptor localization through confocal imaging. Furthermore, the Alexa Fluor 647-labeled conjugate allowed measurement of ligand binding affinities of unlabeled hA2AAR antagonists using a bioluminescence resonance energy transfer (NanoBRET) assay. The fluorescent ligands developed here can therefore be applied to a range of fluorescence-based techniques to further interrogate hA2AAR pharmacology and signaling.

6.
Syst Rev ; 8(1): 309, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31810499

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide epidemic, and while its etiology is polygenic, the role of environmental contaminant exposure in T2DM pathogenesis is of increasing importance. However, the evidence presented in systematic reviews on the relationship between cadmium exposure and T2DM development is inconsistent. This overview aims to assess existing evidence from systematic reviews linking cadmium exposure to T2DM and select metabolic disorders in humans. METHODS: Searches will be conducted in Medline, Embase, Web of Science, GEOBASE, BIOSIS Previews, and Cochrane Database of Systematic Reviews. Two reviewers (J.H and S.T.) will independently complete screening, data abstraction, risk of bias evaluation, and quality assessment. The primary outcome will be the association between cadmium exposure and T2DM prevalence. Secondary outcomes will include prediabetes, obesity, dyslipidemia, hypertension, and non-alcoholic fatty liver disease. We will perform a meta-analysis if two or more studies assess similar populations, utilize analogous methods, have related study designs, and evaluate similar outcomes. DISCUSSION: This overview will assess current evidence from systematic reviews for the association between cadmium exposure and risk of T2DM and other metabolic morbidities. This overview may be helpful for policy-makers and healthcare teams aiming to mitigate T2DM risk in populations at risk of cadmium exposure. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019125956.

7.
Ann Intern Med ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31869834

RESUMO

Background: Preliminary data suggest that preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) may improve risk prediction in patients undergoing noncardiac surgery. Objective: To determine whether preoperative NT-proBNP has additional predictive value beyond a clinical risk score for the composite of vascular death and myocardial injury after noncardiac surgery (MINS) within 30 days after surgery. Design: Prospective cohort study. Setting: 16 hospitals in 9 countries. Patients: 10 402 patients aged 45 years or older having inpatient noncardiac surgery. Measurements: All patients had NT-proBNP levels measured before surgery and troponin T levels measured daily for up to 3 days after surgery. Results: In multivariable analyses, compared with preoperative NT-proBNP values less than 100 pg/mL (the reference group), those of 100 to less than 200 pg/mL, 200 to less than 1500 pg/mL, and 1500 pg/mL or greater were associated with adjusted hazard ratios of 2.27 (95% CI, 1.90 to 2.70), 3.63 (CI, 3.13 to 4.21), and 5.82 (CI, 4.81 to 7.05) and corresponding incidences of the primary outcome of 12.3% (226 of 1843), 20.8% (542 of 2608), and 37.5% (223 of 595), respectively. Adding NT-proBNP thresholds to clinical stratification (that is, the Revised Cardiac Risk Index [RCRI]) resulted in a net absolute reclassification improvement of 258 per 1000 patients. Preoperative NT-proBNP values were also statistically significantly associated with 30-day all-cause mortality (less than 100 pg/mL [incidence, 0.3%], 100 to less than 200 pg/mL [incidence, 0.7%], 200 to less than 1500 pg/mL [incidence, 1.4%], and 1500 pg/mL or greater [incidence, 4.0%]). Limitation: External validation of the identified NT-proBNP thresholds in other cohorts would reinforce our findings. Conclusion: Preoperative NT-proBNP is strongly associated with vascular death and MINS within 30 days after noncardiac surgery and improves cardiac risk prediction in addition to the RCRI. Primary Funding Source: Canadian Institutes of Health Research.

8.
Br J Pharmacol ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31877233

RESUMO

In recent years, several novel aspects of GPCR pharmacology have been described, which are thought to play a role in determining the in vivo efficacy of a compound. Fluorescent ligands have been used to study many of these, which have also required the development of new experimental approaches. Fluorescent ligands offer the potential to use the same fluorescent probe to perform a broad range of experiments, from single-molecule microscopy to in vivo BRET. This review provides an overview of the in vitro use of fluorescent ligands in further understanding emerging pharmacological paradigms within the GPCR field, including ligand-binding kinetics, allosterism and intracellular signalling, along with the use of fluorescent ligands to study physiologically relevant therapeutic agents.

9.
J Am Chem Soc ; 141(45): 17989-17994, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31661269

RESUMO

The nitroxyl radical 1-methyl-2-azaadamantane N-oxyl (Me-AZADO) exhibits magnetic bistability arising from a radical/dimer interconversion. The transition from the rotationally disordered paramagnetic plastic crystal, Me-AZADO, to the ordered diamagnetic crystalline phase, (Me-AZADO)2, has been conclusively demonstrated by crystal structure determination from high-resolution powder diffraction data and by solid-state NMR spectroscopy. The phase change is characterized by a wide thermal hysteresis with high sensitivity to even small applied pressures. The molecular dynamics of the phase transition from the plastic crystal to the conventional crystalline phase has been tracked by solid-state (1H and 13C) NMR and EPR spectroscopies.

10.
Sci Rep ; 9(1): 14219, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578415

RESUMO

The use of CRISPR-Cas9 genome editing to introduce endogenously expressed tags has the potential to address a number of the classical limitations of single molecule localisation microscopy. In this work we present the first systematic comparison of inserts introduced through CRISPR-knock in, with the aim of optimising this approach for single molecule imaging. We show that more highly monomeric and codon optimised variants of mEos result in improved expression at the TubA1B locus, despite the use of identical guides, homology templates, and selection strategies. We apply this approach to target the G protein-coupled receptor (GPCR) CXCR4 and show a further insert dependent effect on expression and protein function. Finally, we show that compared to over-expressed CXCR4, endogenously labelled samples allow for accurate single molecule quantification on ligand treatment. This suggests that despite the complications evident in CRISPR mediated labelling, the development of CRISPR-PALM has substantial quantitative benefits.

11.
Inorg Chem ; 58(21): 14420-14428, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31625735

RESUMO

Two tetranuclear compounds with a cubane-like structure were synthesized from a one-pot reaction between NiII and 2,2,6,6-tetramethyl-3,5-heptanedione (Hdpm) for 1 or 4,4,4-trifluoro-1-phenyl-1,3-butanedione (Hbta) for 2 in the presence of sodium methoxide. The crystal structures of both compounds have been determined by single-crystal X-ray diffraction, and their magnetic properties have been studied by SQUID magnetometry as well as by high-field electron paramagnetic resonance (HFEPR) spectroscopy. For 1, the temperature dependence of the magnetic susceptibility can be fitted by taking into account Ni···Ni ferromagnetic interactions, which leads to an S = 4 ground-state spin. For 2, both antiferromagnetic and ferromagnetic interactions are present. However, the latter are dominant, which also leads to an S = 4 ground-state spin, in good agreement with the HFEPR study.

12.
Mol Pharmacol ; 96(6): 737-752, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31548340

RESUMO

The two G protein-coupled receptors (GPCRs) C-X-C chemokine receptor type 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are part of the class A chemokine GPCR family and represent important drug targets for human immunodeficiency virus (HIV) infection, cancer, and inflammation diseases. CXCR4 is one of only three chemokine receptors with a US Food and Drug Administration approved therapeutic agent, the small-molecule modulator AMD3100. In this review, known modulators of the two receptors are discussed in detail. Initially, the structural relationship between receptors and ligands is reviewed on the basis of common structural motifs and available crystal structures. To date, no atypical chemokine receptor has been crystallized, which makes ligand design and predictions for these receptors more difficult. Next, the selectivity, receptor activation, and the resulting ligand-induced signaling output of chemokines and other peptide ligands are reviewed. Binding of pepducins, a class of lipid-peptides whose basis is the internal loop of a GPCR, to CXCR4 is also discussed. Finally, small-molecule modulators of CXCR4 and ACKR3 are reviewed. These modulators have led to the development of radio- and fluorescently labeled tool compounds, enabling the visualization of ligand binding and receptor characterization both in vitro and in vivo. SIGNIFICANCE STATEMENT: To investigate the pharmacological modulation of CXCR4 and ACKR3, significant effort has been focused on the discovery and development of a range of ligands, including small-molecule modulators, pepducins, and synthetic peptides. Imaging tools, such as fluorescent probes, also play a pivotal role in the field of drug discovery. This review aims to provide an overview of the aforementioned modulators that facilitate the study of CXCR4 and ACKR3 receptors.

13.
Appl Ergon ; 81: 102880, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31422276

RESUMO

The purpose of this study was to quantify biomechanical and cardiovascular exposure while making beds with and without interventions (mattress lift tool and fitted sheet). Sixteen female hotel room cleaners participated in this multifactorial (tool and sheet) laboratory study of crossover design. Exertion in the upper extremity (<2) and back (<3) was consistently lower when using the tool and fitted sheet (p < 0.05). The average number of lifts per bed was reduced by 48% with an 18 s increase in cycle time per bed. Peak forearm flexor activity was significantly lower when using a tool(p < 0.05). Spinal lateral plane range of motion (p < 0.02) and maximum twisting velocity (p < 0.03) were lowest using the tool and fitted sheet together. Interventions such as a mattress lift tool used with a fitted sheet reduced the number of mattress lifts and lowered perceived exertion among hotel room cleaners while making beds.

14.
Br J Hosp Med (Lond) ; 80(8): C120-C123, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31437041

RESUMO

Sepsis-3, published in 2016, defined sepsis as 'life-threatening organ dysfunction caused by a dysregulated host response to infection'. Instead of systemic inflammatory response syndrome (SIRS), calculating the Sequential Organ Failure Assessment (SOFA) score was recommended. The complexity of SOFA also led to the introduction of quick SOFA (qSOFA) as a bedside tool. The simultaneous removal of SIRS and introduction of qSOFA belies their significant differences, with SIRS having a high sensitivity but very low specificity, and qSOFA being very specific for a poor outcome, but having a lower sensitivity than SIRS. In the UK, the variables within qSOFA are collected on a regular and repeated basis, along with additional variables, as part of the National Early Warning Score (NEWS). A knowledge of SIRS, qSOFA and NEWS is of value in assessing patients with suspected sepsis, as discussed in this article.

15.
Chem Sci ; 10(25): 6354-6361, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31341591

RESUMO

The magnetic properties of 3d monometallic complexes can be tuned through geometric control, owing to their synthetic accessibility and relative structural simplicity. Monodentate ligands offer great potential for fine-tuning the coordination environment to engineer both the axial and rhombic zero-field splitting (ZFS) parameters. In [CoCl3(DABCO)(HDABCO)] (1), the trigonal bipyramidal Co(ii) centre has two bulky axial ligands and three equatorial chloride ligands. An in-depth experimental and theoretical study of 1 reveals a large easy-plane magnetic anisotropy (+ve D) with a negligible rhombic zero-field splitting (E) due to the strict axial symmetry imposed by the C 3 symmetric ligand and trigonal space group. The large easy-plane magnetic anisotropy (D = +44.5 cm-1) is directly deduced using high-field EPR and frequency-domain magnetic resonance (FDMR) studies. Ab initio calculations reveal a large positive contribution to the D term arising from ground state/excited state mixing of the 4E'' states at ∼4085 cm-1 and a minor contribution from the spin-flip transition as well. The nature of the slow relaxation in 1 is elucidated through analysis of the rates of relaxation of magnetisation, taking into account Raman and direct spin-lattice relaxation processes and Quantum Tunnelling of the Magnetisation (QTM). The terms relating to the direct process and QTM were found based on the fit of the field-dependence of τ at 2 K. Subsequently, these were used as fixed parameters in the fit of the temperature-dependence of τ to obtain the Raman terms. This experimental-theoretical investigation provides further insight into the power of FDMR and ab initio methods for the thorough investigation of magnetic anisotropy. Thus, these results contribute to design criteria for high magnetic anisotropy systems.

16.
Dalton Trans ; 48(41): 15560-15566, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31342029

RESUMO

Structural, magnetic and spectroscopic data of four complex salts, [Mn(napsal2323)]NTf2, 1,[Mn(napsal2323)]ClO4, 2, [Mn(napsal2323)]BF4, 3 and [Mn(napsal2323)]NO3, 4, of the [Mn(napsal2323)]+ complex cation indicate that the Mn3+ ion is stabilized in the rare S = 1 spin triplet form in this ligand sphere. Zero-field splitting values of D = +19.6 cm-1 and |E| = 2.02 cm-1 for complex 1 were obtained by High Field Electron Paramagnetic Resonance (HFEPR) measurements conducted over a range of frequencies. Structural and magnetic data also indicate that co-crystallization of complexes 2 and 3 with 0.5 equivalents of ethanol yields the high spin S = 2 forms of the perchlorate and tetrafluoroborate solvates [Mn(napsal2323)]ClO4·0.5(C2H5OH), 2·0.5EtOH and [Mn(napsal2323)]BF4·0.5(C2H5OH), 3·0.5EtOH.

17.
Phys Chem Chem Phys ; 21(38): 21200-21204, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31310269

RESUMO

Dynamic Nuclear Polarization (DNP) can increase the sensitivity of Nuclear Magnetic Resonance (NMR), but it is challenging in the liquid state at high magnetic fields. In this study we demonstrate significant enhancements of NMR signals (up to 70 on 13C) in the liquid state by scalar Overhauser DNP at 14.1 T, with high resolution (∼0.1 ppm) and relatively large sample volume (∼100 µL).

18.
J Am Chem Soc ; 141(30): 11970-11975, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31283232

RESUMO

Structural and spectroscopic characterization of the dimeric iron hydride complex [Ph2B(tBuIm)2FeH]2 reveals an unusual structure in which a tetrahedral iron(II) site (S = 2) is connected to a square planar iron(II) site (S = 1) by two bridging hydride ligands. Magnetic susceptibility reveals strong ferromagnetic coupling between iron centers, with a coupling constant of J = +110(12) cm-1, to give an S = 3 ground state. High-frequency and -field electron paramagnetic resonance (HFEPR) spectroscopy confirms this model. A qualitative molecular orbital analysis of the electronic structure, as supported by electronic structure calculations, reveals that the observed spin configuration results from the orthogonal alignment of two geometrically distinct four-coordinate iron fragments held together by highly covalent hydride ligands.

19.
Br J Pharmacol ; 176(17): 3220-3235, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31162634

RESUMO

BACKGROUND AND PURPOSE: Vascular endothelial growth factor A (VEGF-A) is a key mediator of angiogenesis. A striking feature of the binding of a fluorescent analogue of VEGF165 a to nanoluciferase-tagged VEGF receptor 2 (VEGFR2) in living cells is that the BRET signal is not sustained and declines over time. This may be secondary to receptor internalisation. Here, we have compared the binding of three fluorescent VEGF-A isoforms to VEGFR2 in cells and isolated membrane preparations. EXPERIMENTAL APPROACH: Ligand-binding kinetics were monitored in both intact HEK293T cells and membranes (expressing nanoluciferase-tagged VEGFR2) using BRET between tagged receptor and fluorescent analogues of VEGF165 a, VEGF165 b, and VEGF121 a. VEGFR2 endocytosis in intact cells expressing VEGFR2 was monitored by following the appearance of fluorescent ligand-associated receptors in intracellular endosomes using automated quantitative imaging. KEY RESULTS: Quantitative analysis of the effect of fluorescent VEGF-A isoforms on VEGFR2 endocytosis in cells demonstrated that they produce a rapid and potent translocation of ligand-bound VEGFR2 into intracellular endosomes. NanoBRET can be used to monitor the kinetics of the binding of fluorescent VEGF-A isoforms to VEGFR2. In isolated membrane preparations, ligand-binding association curves were maintained for the duration of the 90-min experiment. Measurement of the koff at pH 6.0 in membrane preparations indicated shorter ligand residence times than those obtained at pH 7.4. CONCLUSIONS AND IMPLICATIONS: These studies suggest that rapid VEGF-A isoform-induced receptor endocytosis shortens agonist residence times on the receptor (1/koff ) as VEGFR2 moves from the plasma membrane to the intracellular endosomes.

20.
Mol Pharmacol ; 96(6): 778-793, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31092552

RESUMO

G protein-coupled receptors (GPCRs) are regulated by complex molecular mechanisms, both in physiologic and pathologic conditions, and their signaling can be intricate. Many factors influence their signaling behavior, including the type of ligand that activates the GPCR, the presence of interacting partners, the kinetics involved, or their location. The two CXC-type chemokine receptors, CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), both members of the GPCR superfamily, are important and established therapeutic targets in relation to cancer, human immunodeficiency virus infection, and inflammatory diseases. Therefore, it is crucial to understand how the signaling of these receptors works to be able to specifically target them. In this review, we discuss how the signaling pathways activated by CXCR4 and ACKR3 can vary in different situations. G protein signaling of CXCR4 depends on the cellular context, and discrepancies exist depending on the cell lines used. ACKR3, as an atypical chemokine receptor, is generally reported to not activate G proteins but can broaden its signaling spectrum upon heteromerization with other receptors, such as CXCR4, endothelial growth factor receptor, or the α 1-adrenergic receptor (α 1-AR). Also, CXCR4 forms heteromers with CC chemokine receptor (CCR) 2, CCR5, the Na+/H+ exchanger regulatory factor 1, CXCR3, α 1-AR, and the opioid receptors, which results in differential signaling from that of the monomeric subunits. In addition, CXCR4 is present on membrane rafts but can go into the nucleus during cancer progression, probably acquiring different signaling properties. In this review, we also provide an overview of the currently known critical amino acids involved in CXCR4 and ACKR3 signaling.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA