130,430 research outputs found
Truncation of the receptor impairs agonist-induced phosphorylation and desensitization of the alpha1B-adrenergic receptor
No full textA-Kinase-Anchoring Protein-Lbc Anchors IκB Kinase β To Support Interleukin-6-Mediated Cardiomyocyte Hypertrophy.
No full textIn response to stress, the heart undergoes a pathological remodeling process associated with hypertrophy and the reexpression of a fetal gene program that ultimately causes cardiac dysfunction and heart failure. In this study, we show that A-kinase-anchoring protein (AKAP)-Lbc and the inhibitor of NF-κB kinase subunit β (IKKβ) form a transduction complex in cardiomyocytes that controls the production of proinflammatory cytokines mediating cardiomyocyte hypertrophy. In particular, we can show that activation of IKKβ within the AKAP-Lbc complex promotes NF-κB-dependent production of interleukin-6 (IL-6), which in turn enhances fetal gene expression and cardiomyocyte growth. These findings provide a new mechanistic hypothesis explaining how hypertrophic signals are coordinated and conveyed to interleukin-mediated transcriptional reprogramming events in cardiomyocytes
Characterization of the phosphorylation sites involved in G protein-coupled receptor kinase- and protein kinase C-mediated desensitization of the alpha1B-adrenergic receptor
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Anchoring of both PKA and 14-3-3 inhibits the Rho-GEF activity of the AKAP-Lbc signaling complex
No full textDirect interaction of ezrin with the alpha1b-adrenergic receptor regulates recycling of the internalized receptors
No full textStrain energy density approach as fatigue assessment of Ti6Al4V specimens machined by WEDM single step technology
No full textThe present paper summarizes the results from force-controlled fatigue tests performed on Ti6Al4V specimens machined by wire electrical discharge machining (WEDM) single step technology. For this aim, blunt V-notched specimens with various notch root radii and un-notched “dog bone” specimens are considered. The fatigue behaviour of this alloy machined by WEDM single step technology is an extremely important issue but, despite this, the literature on this topic is very poor and the effect of geometrical discontinuities on the fatigue life of has still to be investigated. Fatigue data, generated by testing a total number of 62 specimen, are re-analysed by means of the Strain Energy Density (SED) method, investigating the possibility to use this method following a numerical approach. Estimation of the critical radius is performed on the basis of finite element analysis to overcome the lack of knowledge of the material properties often related to the machining process. Thanks to the SED method, it is possible to summarize in a single scatter-band all the collected fatigue data, independently of the specimen geometry. The proposed numerical approach is capable to reduce the scatter index compared to the actual procedure with modest extra effort, also solving the issue related to the geometry selection for the critical radius identification. The method is successfully validated by assessing the fatigue life of specimens with two notch geometries not considered during the critical radius identification. © 2022 The Author(s
Structural determinants involved in the activation and regulation of G protein-coupled receptors: lessons from the alpha1-adrenegic receptor subtypes
No full textThe aim of a large number of studies on G protein-coupled receptors was centered on understanding the structural basis of their main functional properties. Here, we will briefly review the results obtained on the alpha1-adrenergic receptor subtypes belonging to the rhodopsin-like family of receptors. These findings contribute, on the one hand, to further understand the molecular basis of adrenergic transmission and, on the other, to provide some generalities on the structure-functional relationship of G protein-coupled receptors
Molecular mechanisms involved in the activation and regulation of the alpha 1-adrenergic receptor subtypes
No full textThe adrenergic receptors (ARs) belong to the superfamily of membrane-bound G protein coupled receptors (GPCRs). Our investigation has focused on the structure-function relationship of the alpha 1b-AR subtype used as the model system for other GPCRs. Site-directed mutagenesis studies have elucidated the structural domains of the alpha 1b-AR involved in ligand binding, G protein coupling or desensitization. In addition, a combined approach using site-directed mutagenesis and molecular dynamics analysis of the alpha 1b-AR has provided information about the potential mechanisms underlying the activation process of the receptor, i.e. its transition from the 'inactive' to the 'active' conformation
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