Kinetic analysis of endogenous β<sub>2</sub>‐adrenoceptor‐mediated cAMP GloSensor™ responses in HEK293 cells

Cullum, Sean A; Veprintsev, Dmitry B.; Hill, Stephen J.

doi:10.1111/bph.16008

Cited by 4 publications

(1 citation statement)

References 56 publications

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“…HEK293-F cells have been used to produce several FDA-approved therapeutics, including recombinant FVIII fusion protein (rFVIIIFc) (Elosta®) and glucagon-like peptide 1 receptor agonist (Dulaglutide; Trulicity®) for the treatment of hemophilia A and type 2 diabetes, respectively. HEK293G cells (Promega, USA) stably express cAMP GloSensor™ (20F) biosensor [66].…”

Section: Expression Systems and Approaches To Production Of Bispecifi...mentioning

confidence: 99%

State-of-the-Art Approaches to Heterologous Expression of Bispecific Antibodies Targeting Solid Tumors

Misorin,

Chernyshova,

Karbyshev

2023

Biochemistry Moscow

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Bispecific antibodies (bsAbs) are some of the most promising biotherapeutics due to the versatility provided by their structure and functional features. bsAbs simultaneously bind two antigens or two epitopes on the same antigen. Moreover, they are capable of directing immune effector cells to cancer cells and delivering various compounds (radionuclides, toxins, and immunologic agents) to the target cells, thus offering a broad spectrum of clinical applications. Current review is focused on the technologies used in bsAb engineering, current progress and prospects of these antibodies, and selection of various heterologous expression systems for bsAb production. We also discuss the platforms development of bsAbs for the therapy of solid tumors.

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Section: Expression Systems and Approaches To Production Of Bispecifi...mentioning

confidence: 99%

State-of-the-Art Approaches to Heterologous Expression of Bispecific Antibodies Targeting Solid Tumors

Misorin,

Chernyshova,

Karbyshev

2023

Biochemistry Moscow

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Beta-2 adrenergic receptor agonism alters astrocyte phagocytic activity and has potential applications to psychiatric disease

Bowen,

DiGiacomo,

Fraser

et al. 2023

Discov Ment Health

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Schizophrenia is a debilitating condition necessitating more efficacious therapies. Previous studies suggested that schizophrenia development is associated with aberrant synaptic pruning by glial cells. We pursued an interdisciplinary approach to understand whether therapeutic reduction in glial cell—specifically astrocytic—phagocytosis might benefit neuropsychiatric patients. We discovered that beta-2 adrenergic receptor (ADRB2) agonists reduced phagocytosis using a high-throughput, phenotypic screen of over 3200 compounds in primary human fetal astrocytes. We used protein interaction pathways analysis to associate ADRB2, to schizophrenia and endocytosis. We demonstrated that patients with a pediatric exposure to salmeterol, an ADRB2 agonist, had reduced in-patient psychiatry visits using a novel observational study in the electronic health record. We used a mouse model of inflammatory neurodegenerative disease and measured changes in proteins associated with endocytosis and vesicle-mediated transport after ADRB2 agonism. These results provide substantial rationale for clinical consideration of ADRB2 agonists as possible therapies for patients with schizophrenia.

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Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists

Cullum,

Platt,

Dale

et al. 2024

Commun Biol

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The concept of agonist-independent signalling that can be attenuated by inverse agonists is a fundamental element of the cubic ternary complex model of G protein-coupled receptor (GPCR) activation. This model shows how a GPCR can exist in two conformational states in the absence of ligands; an inactive R state and an active R* state that differ in their affinities for agonists, inverse agonists, and G-protein alpha subunits. The proportion of R* receptors that exist in the absence of agonists determines the level of constitutive receptor activity. In this study we demonstrate that mechanical stimulation can induce β2-adrenoceptor agonist-independent Gs-mediated cAMP signalling that is sensitive to inhibition by inverse agonists such as ICI-118551 and propranolol. The size of the mechano-sensitive response is dependent on the cell surface receptor expression level in HEK293G cells, is still observed in a ligand-binding deficient D113A mutant β2-adrenoceptor and can be attenuated by site-directed mutagenesis of the extracellular N-glycosylation sites on the N-terminus and second extracellular loop of the β2-adrenoceptor. Similar mechano-sensitive agonist-independent responses are observed in HEK293G cells overexpressing the A2A-adenosine receptor. These data provide new insights into how agonist-independent constitutive receptor activity can be enhanced by mechanical stimulation and regulated by inverse agonists.

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Kinetic analysis of endogenous β₂‐adrenoceptor‐mediated cAMP GloSensor™ responses in HEK293 cells

Cited by 4 publications

References 56 publications

State-of-the-Art Approaches to Heterologous Expression of Bispecific Antibodies Targeting Solid Tumors

State-of-the-Art Approaches to Heterologous Expression of Bispecific Antibodies Targeting Solid Tumors

Beta-2 adrenergic receptor agonism alters astrocyte phagocytic activity and has potential applications to psychiatric disease

Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists

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Kinetic analysis of endogenous β2‐adrenoceptor‐mediated cAMP GloSensor™ responses in HEK293 cells

Cited by 4 publications

References 56 publications

State-of-the-Art Approaches to Heterologous Expression of Bispecific Antibodies Targeting Solid Tumors

State-of-the-Art Approaches to Heterologous Expression of Bispecific Antibodies Targeting Solid Tumors

Beta-2 adrenergic receptor agonism alters astrocyte phagocytic activity and has potential applications to psychiatric disease

Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists

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Product

Resources

About

Kinetic analysis of endogenous β₂‐adrenoceptor‐mediated cAMP GloSensor™ responses in HEK293 cells