Hydrogenated alprenolol derivative where the extra hydrogens are often tritiated. This radiolabeled form of ALPRENOLOL, a beta-adrenergic blocker, is used to label the beta-adrenergic receptor for isolation and study.
One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.
Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction.
A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.
Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.
A beta-2 selective adrenergic antagonist. It is used primarily in animal and tissue experiments to characterize BETA-2 ANDRENERGIC RECEPTORS.
Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.
Drugs that selectively bind to and activate beta-adrenergic receptors.
G-protein-coupled receptor kinases that mediate agonist-dependent PHOSPHORYLATION and desensitization of BETA-ADRENERGIC RECEPTORS.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-2 receptors are more sensitive to EPINEPHRINE than to NOREPINEPHRINE and have a high affinity for the agonist TERBUTALINE. They are widespread, with clinically important roles in SKELETAL MUSCLE; LIVER; and vascular, bronchial, gastrointestinal, and genitourinary SMOOTH MUSCLE.
A ubiquitously expressed G-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of BETA-ADRENERGIC RECEPTORS. It may play an essential role in regulating myocardial contractile response.
A family of serine-threonine kinases that are specific for G-PROTEIN-COUPLED RECEPTORS. They are regulatory proteins that play a role in G-protein-coupled receptor densensitization.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.
A G-protein-coupled receptor kinase subtype that is primarily expressed in the MYOCARDIUM and may play a role in the regulation of cardiac functions.
Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.
The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC
A ubiquitously expressed G-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of BETA-ADRENERGIC RECEPTORS and a variety of other G-PROTEIN-COUPLED RECEPTORS. Although it is highly homologous to G-PROTEIN-COUPLED RECEPTOR KINASE 2, it is not considered to play an essential role in regulating myocardial contractile response.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-1 receptors are equally sensitive to EPINEPHRINE and NOREPINEPHRINE and bind the agonist DOBUTAMINE and the antagonist METOPROLOL with high affinity. They are found in the HEART, juxtaglomerular cells, and in the central and peripheral nervous systems.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.
A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The beta-3 adrenergic receptors are the predominant beta-adrenergic receptor type expressed in white and brown ADIPOCYTES and are involved in modulating ENERGY METABOLISM and THERMOGENESIS.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A PROTEIN-SERINE-THREONINE KINASE that is found in PHOTORECEPTOR CELLS. It mediates light-dependent PHOSPHORYLATION of RHODOPSIN and plays an important role in PHOTOTRANSDUCTION.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Compounds bind to and activate ADRENERGIC BETA-2 RECEPTORS.
A G-protein-coupled receptor kinase subtype that is primarily expressed in the TESTES and BRAIN. Variants of this subtype exist due to multiple alternative splicing of its mRNA.
Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors.
Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Drugs that selectively bind to and activate alpha adrenergic receptors.
Agents that inhibit PROTEIN KINASES.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Established cell cultures that have the potential to propagate indefinitely.
Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.
A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION.
AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.
The rate dynamics in chemical or physical systems.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Drugs that bind to and activate adrenergic receptors.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.
Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.
Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
Compounds that bind to and activate ADRENERGIC ALPHA-1 RECEPTORS.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Compounds that bind to and activate ADRENERGIC BETA-1 RECEPTORS.
A highly selective and specific beta antagonist that is used to characterize beta-adrenoceptors.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Proteins prepared by recombinant DNA technology.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638)
The relationship between the dose of an administered drug and the response of the organism to the drug.
Drugs that bind to and block the activation of ADRENERGIC BETA-1 RECEPTORS.
An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
A benzodioxane-linked imidazole that has alpha-2 adrenoceptor antagonist activity.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
1,4-Diethylene dioxides. Industrial solvents. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), dioxane itself may "reasonably be anticipated to be a carcinogen." (Merck Index, 11th ed)
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
Elements of limited time intervals, contributing to particular results or situations.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Drugs that bind to and block the activation of ADRENERGIC BETA-3 RECEPTORS.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
Plant steroids ubiquitously distributed throughout the plant kingdom. They play essential roles in modulating growth and differentiation of cells at nanomolar to micromolar concentrations.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.
A substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A cell line derived from cultured tumor cells.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.
A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.
Steroidal compounds in which one or more carbon atoms in the steroid ring system have been substituted with non-carbon atoms.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
A family of heterotrimeric GTP-binding protein alpha subunits that activate ADENYLYL CYCLASES.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
A purplish-red, light-sensitive pigment found in RETINAL ROD CELLS of most vertebrates. It is a complex consisting of a molecule of ROD OPSIN and a molecule of 11-cis retinal (RETINALDEHYDE). Rhodopsin exhibits peak absorption wavelength at about 500 nm.
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
One of the ADRENERGIC BETA-ANTAGONISTS used as an antihypertensive, anti-anginal, and anti-arrhythmic agent.
A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.
Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters.
A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
GTP-BINDING PROTEINS that contain three non-identical subunits. They are found associated with members of the seven transmembrane domain superfamily of G-PROTEIN-COUPLED RECEPTORS. Upon activation the GTP-BINDING PROTEIN ALPHA SUBUNIT of the complex dissociates leaving a dimer of a GTP-BINDING PROTEIN BETA SUBUNIT bound to a GTP-BINDING PROTEIN GAMMA SUBUNIT.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Transport proteins that carry specific substances in the blood or across cell membranes.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.

Real-time visualization of the cellular redistribution of G protein-coupled receptor kinase 2 and beta-arrestin 2 during homologous desensitization of the substance P receptor. (1/425)

The substance P receptor (SPR) is a G protein-coupled receptor (GPCR) that plays a key role in pain regulation. The SPR desensitizes in the continued presence of agonist, presumably via mechanisms that implicate G protein-coupled receptor kinases (GRKs) and beta-arrestins. The temporal relationship of these proposed biochemical events has never been established for any GPCR other than rhodopsin beyond the resolution provided by biochemical assays. We investigate the real-time activation and desensitization of the human SPR in live HEK293 cells using green fluorescent protein conjugates of protein kinase C, GRK2, and beta-arrestin 2. The translocation of protein kinase C betaII-green fluorescent protein to and from the plasma membrane in response to substance P indicates that the human SPR becomes activated within seconds of agonist exposure, and the response desensitizes within 30 s. This desensitization process coincides with a redistribution of GRK2 from the cytosol to the plasma membrane, followed by a robust redistribution of beta-arrestin 2 and a profound change in cell morphology that occurs after 1 min of SPR stimulation. These data establish a role for GRKs and beta-arrestins in homologous desensitization of the SPR and provide the first visual and temporal resolution of the sequence of events underlying homologous desensitization of a GPCR in living cells.  (+info)

Regulation of G protein-coupled receptor kinases by caveolin. (2/425)

G protein-coupled receptor kinases (GRKs) have been principally characterized by their ability to phosphorylate and desensitize G protein-coupled receptors. However, recent studies suggest that GRKs may have more diverse protein/protein interactions in cells. Based on the identification of a consensus caveolin binding motif within the pleckstrin homology domain of GRK2, we tested the direct binding of purified full-length GRK2 to various glutathione S-transferase-caveolin-1 fusion proteins, and we discovered a specific interaction of GRK2 with the caveolin scaffolding domain. Interestingly, analysis of GRK1 and GRK5, which lack a pleckstrin homology domain, revealed in vitro binding properties similar to those of GRK2. Maltose-binding protein caveolin and glutathione S-transferase-GRK fusion proteins were used to map overlapping regions in the N termini of both GRK2 and GRK5 that appear to mediate conserved GRK/caveolin interactions. In vivo association of GRK2 and caveolin was suggested by co-fractionation of GRK2 with caveolin in A431 and NIH-3T3 cells and was further supported by co-immunoprecipitation of GRK2 and caveolin in COS-1 cells. Functional significance for the GRK/caveolin interaction was demonstrated by the potent inhibition of GRK-mediated phosphorylation of both receptor and peptide substrates by caveolin-1 and -3 scaffolding domain peptides. These data reveal a novel mode for the regulation of GRKs that is likely to play an important role in their cellular function.  (+info)

Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus. (3/425)

The binding of CC chemokines to CC chemokine receptor 5 (CCR5) triggers cellular responses that, generally, are only transient in nature. To explore the potential role of G protein-coupled receptor kinases (GRKs) in the regulation of CCR5, we performed phosphorylation experiments in a rat basophilic leukemia cell line stably expressing CCR5. The ability of various CCR5 ligands to stimulate calcium mobilization in these cells correlated with their ability to induce receptor phosphorylation, desensitization, internalization, and GRK association with the receptor. Aminooxypentane-RANTES, a potent inhibitor of human immunodeficiency virus infection, has been proposed to act through enhanced CCR5 internalization and inhibition of receptor recycling. Aminooxypentane-RANTES profoundly induced CCR5 phosphorylation, but had no effect on CCR1. In permeabilized rat basophilic leukemia CCR5 cells, monoclonal antibodies with specificity for GRK2/3 inhibited RANTES-induced receptor phosphorylation. Consistent with a role for these kinases in CCR5 regulation, 1-2 x 10(5) copies of GRK2 or GRK3 were found to be expressed in peripheral blood leukocytes. Phosphoamino acid analysis revealed that RANTES-induced CCR5 phosphorylation selectively occurs on serine residues. Our findings with receptor mutants indicate that serine residues at positions 336, 337, 342, and 349 represent GRK phosphorylation sites on CCR5. This study demonstrates that chemokines differ in their ability to induce CCR5 phosphorylation and desensitization and provides a molecular mechanism for the agonist-induced attenuation of CCR5 signaling.  (+info)

Sequestration of dopamine D2 receptors depends on coexpression of G-protein-coupled receptor kinases 2 or 5. (4/425)

We examined the agonist-dependent sequestration/internalization of dopamine D2 receptor (the long form D2L and short form D2S), which were transiently expressed in COS-7 and HEK 293 cells with or without G-protein-coupled receptor kinases (GRK2 or GRK5). Sequestration was assessed quantitatively by loss of [3H] sulpiride-binding activity from the cell surface and by transfer of [3H] spiperone-binding activity from the membrane fraction to the light vesicle fraction in sucrose-density gradients. In COS-7 cells expressing D2 receptors alone, virtually no sequestration was observed with or without dopamine (< 4%). When GRK2 was coexpressed, 50% of D2S receptors and 36% of D2L receptors were sequestered by treatment with 10(-4) M dopamine for 2 h, whereas no sequestration was observed in cells expressing the dominant negative form of GRK2 (DN-GRK2). When GRK5 was coexpressed, 36% of D2S receptors were sequestered following the same treatment. The agonist-dependent and GRK2-dependent sequestration of D2S receptors was reduced markedly in the presence of hypertonic medium containing 0.45 M sucrose, suggesting that the sequestration follows the clathrin pathway. Internalization of D2S receptors was also assessed by immunofluorescence confocal microscopy. Translocation of D2 receptors from the cell membrane to intracellular vesicles was observed following the treatment with dopamine from HEK 293 cells only when GRK2 was coexpressed. D2S receptors expressed in HEK 293 cells were shown to be phosphorylated by GRK2 in an agonist-dependent manner. These results indicate that the sequestration of D2 receptors occurs only through a GRK-mediated pathway.  (+info)

The absence of a direct correlation between the loss of [D-Ala2, MePhe4,Gly5-ol]Enkephalin inhibition of adenylyl cyclase activity and agonist-induced mu-opioid receptor phosphorylation. (5/425)

Chronic activation of the mu-opioid receptor (MOR1TAG) results in the loss of agonist response that has been attributed to desensitization and down-regulation of the receptor. It has been suggested that opioid receptor phosphorylation is the mechanism by which this desensitization and down-regulation occurs. When MOR1TAG was stably expressed in both neuroblastoma neuro2A and human embryonic kidney HEK293 cells, the opioid agonist [D-Ala2,MePhe4, Gly5-ol]enkephalin (DAMGO) induced a time- and concentration-dependent phosphorylation of the receptor, in both cell lines, that could be reversed by the antagonist naloxone. Protein kinase C can phosphorylate the receptor, but is not involved in DAMGO-induced MOR1TAG phosphorylation. The rapid rate of receptor phosphorylation, occurring within minutes, did not correlate with the rate of the loss of agonist-mediated inhibition of adenylyl cyclase, which occurs in hours. This lack of correlation between receptor phosphorylation and the loss of response was further demonstrated when receptor phosphorylation was increased by either calyculin A or overexpression of the G-protein receptor kinases. Calyculin A increased the magnitude of MOR1TAG phosphorylation without altering the DAMGO-induced loss of the adenylyl cyclase response. Similarly, when mu- and delta-opioid (DOR1TAG) receptors were expressed in the same system, overexpression of beta-adrenergic receptor kinase 2 elevated agonist-induced phosphorylation for both receptors. However, in the same cell lines under the same conditions, overexpression of beta-adrenergic receptor kinase 2 and beta-arrestin 2 accelerated the rate of DPDPE- but not DAMGO-induced receptor desensitization. Thus, these data show that phosphorylation of MOR1TAG is not an obligatory event for the DAMGO-induced loss in the adenylyl cyclase regulation by the receptor.  (+info)

Both Gs and Gi proteins are critically involved in isoproterenol-induced cardiomyocyte hypertrophy. (6/425)

Activation of beta-adrenoreceptors induces cardiomyocyte hypertrophy. In the present study, we examined isoproterenol-evoked intracellular signal transduction pathways leading to activation of extracellular signal-regulated kinases (ERKs) and cardiomyocyte hypertrophy. Inhibitors for cAMP and protein kinase A (PKA) abolished isoproterenol-evoked ERK activation, suggesting that Gs protein is involved in the activation. Inhibition of Gi protein by pertussis toxin, however, also suppressed isoproterenol-induced ERK activation. Overexpression of the Gbetagamma subunit binding domain of the beta-adrenoreceptor kinase 1 and of COOH-terminal Src kinase, which inhibit functions of Gbetagamma and the Src family tyrosine kinases, respectively, also inhibited isoproterenol-induced ERK activation. Overexpression of dominant-negative mutants of Ras and Raf-1 kinase and of the beta-adrenoreceptor mutant that lacks phosphorylation sites by PKA abolished isoproterenol-stimulated ERK activation. The isoproterenol-induced increase in protein synthesis was also suppressed by inhibitors for PKA, Gi, tyrosine kinases, or Ras. These results suggest that isoproterenol induces ERK activation and cardiomyocyte hypertrophy through two different G proteins, Gs and Gi. cAMP-dependent PKA activation through Gs may phosphorylate the beta-adrenoreceptor, leading to coupling of the receptor from Gs to Gi. Activation of Gi activates ERKs through Gbetagamma, Src family tyrosine kinases, Ras, and Raf-1 kinase.  (+info)

Decreased expression and activity of G-protein-coupled receptor kinases in peripheral blood mononuclear cells of patients with rheumatoid arthritis. (7/425)

Beta2-Adrenergic and chemokine receptor antagonists delay the onset and reduce the severity of joint injury in rheumatoid arthritis. beta2-Adrenergic and chemokine receptors belong to the G-protein-coupled receptor family whose responsiveness is turned off by the G-protein-coupled receptor kinase family (GRK-1 to 6). GRKs phosphorylate receptors in an agonist-dependent manner resulting in receptor/G-protein uncoupling via subsequent binding of arrestin proteins. We assessed the activity of GRKs in lymphocytes of rheumatoid arthritis (RA) patients by rhodopsin phosphorylation. We found a significant decrease in GRK activity in RA subjects that is mirrored by a decrease in GRK-2 protein expression. Moreover, GRK-6 protein expression is reduced in RA patients whereas GRK-5 protein levels were unchanged. In search of an underlying mechanism, we demonstrated that proinflammatory cytokines induce a decrease in GRK-2 protein levels in leukocytes from healthy donors. Since proinflammatory cytokines are abundantly expressed in RA, it may provide an explanation for the decrease in GRK-2 expression and activity in patients. No changes in beta2-adrenergic receptor number and Kd were detected. However, RA patients showed a significantly increased cAMP production and inhibition of TNF-alpha production by beta2-adrenergic stimulation, suggesting that reduced GRK activity is associated with increased sensitivity to beta2-adrenergic activation.  (+info)

Targeting Gbeta gamma signaling in arterial vascular smooth muscle proliferation: a novel strategy to limit restenosis. (8/425)

Restenosis continues to be a major problem limiting the effectiveness of revascularization procedures. To date, the roles of heterotrimeric G proteins in the triggering of pathological vascular smooth muscle (VSM) cell proliferation have not been elucidated. betagamma subunits of heterotrimeric G proteins (Gbetagamma) are known to activate mitogen-activated protein (MAP) kinases after stimulation of certain G protein-coupled receptors; however, their relevance in VSM mitogenesis in vitro or in vivo is not known. Using adenoviral-mediated transfer of a transgene encoding a peptide inhibitor of Gbetagamma signaling (betaARKct), we evaluated the role of Gbetagamma in MAP kinase activation and proliferation in response to several mitogens, including serum, in cultured rat VSM cells. Our results include the striking finding that serum-induced proliferation of VSM cells in vitro is mediated largely via Gbetagamma. Furthermore, we studied the effects of in vivo adenoviral-mediated betaARKct gene transfer on VSM intimal hyperplasia in a rat carotid artery restenosis model. Our in vivo results demonstrated that the presence of the betaARKct in injured rat carotid arteries significantly reduced VSM intimal hyperplasia by 70%. Thus, Gbetagamma plays a critical role in physiological VSM proliferation, and targeted Gbetagamma inhibition represents a novel approach for the treatment of pathological conditions such as restenosis.  (+info)

The beta-adrenergic receptor kinase (beta ARK) phosphorylates the agonist-occupied beta-adrenergic receptor to promote rapid receptor uncoupling from Gs, thereby attenuating adenylyl cyclase activity. Beta ARK-mediated receptor desensitization may reflect a general molecular mechanism operative on many G-protein-coupled receptor systems and, particularly, synaptic neurotransmitter receptors. Two distinct cDNAs encoding beta ARK isozymes were isolated from rat brain and sequenced. The regional and cellular distributions of these two gene products, termed beta ARK1 and beta ARK2, were determined in brain by in situ hybridization and by immunohistochemistry at the light and electron microscopic levels. The beta ARK isozymes were found to be expressed primarily in neurons distributed throughout the CNS. Ultrastructurally, beta ARK1 and beta ARK2 immunoreactivities were present both in association with postsynaptic densities and, presynaptically, with axon terminals. The beta ARK isozymes have a ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Agonist-induced phosphorylation has been demonstrated for a variety of GPCRs including the β-adrenergic (Ferguson et al., 1995; Freedman et al., 1995; Fredericks et al., 1996; January et al., 1997), α-adrenergic (Easonet al., 1995), δ-opioid (Pei et al., 1995), endothelin (Freedman et al., 1997), adenosine (Palmeret al., 1995), vasopressin (Innamorati et al., 1997), and somatostatin (Hipkin et al., 1997) receptors. However, there have been relatively few unequivocal reports of AT1-R phosphorylation. This has been due in large part to the inability to distinguish the immunoprecipitated phospho-AT1-R from more abundant phosphoproteins that either genuinely or spuriously coprecipitate with the receptor (Smith et al., 1998). Despite these problems, unequivocal agonist-induced phosphorylation of a transiently expressed epitope-tagged AT1-R (Oppermann et al., 1996), and of a stably expressed (His)6-tagged AT1-R (Balmforth et al., 1997) has been reported in human embryonic kidney 293 cells. We ...
In this study, we have examined the potential roles of GRK3 and -6 in the phosphorylation and desensitization of M3 mACh receptors endogenously expressed in human SH-SY5Y neuroblastoma cells. Previous studies have established that not only the M2 and M4adenylyl cyclase-linked, but also the Gαq/11PLC-coupled M1/M3 mACh receptors are in vitro substrates for GRK2 and -3 (DebBurman et al., 1995; Haga et al., 1996). However, in the absence of direct evidence for such a role of these GRKs in intact cells, this area remains controversial. Indeed, in a series of studies from these laboratories, recombinant M3 mACh receptors expressed in CHO cells have been shown to undergo rapid agonist-dependent phosphorylation on serines in the third intracellular loop and furthermore that recombinant casein kinase 1α can enhance this phosphorylation in membrane preparations (Tobin et al., 1997). More recent studies have revealed that a dominant negative mutant of this kinase can partially suppress agonist-mediated ...
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Our data demonstrate the novel finding that GRK5 activity attenuates atherosclerosis, and that it does so through distinct antiatherogenic mechanisms in ECs, SMCs, monocytes, and Mϕs. These cell-specific mechanisms encompass diverse signaling systems, including the receptor tyrosine kinases CSF-1R and PDGFRβ, the 7-transmembrane receptor CCR2, the innate immunity receptors TLR4 and TNFR1, and the transcription factor NF-κB. Thus, despite data from overexpression and model cell systems suggesting the possibility that GRK5 could mediate proatherogenic activities,9,11,13,14 net physiological GRK5 activity clearly appears to be antiatherogenic.. Because GRK5-mediated phosphorylation of 7-transmembrane receptors promotes receptor/β-arrestin association,1 it may seem paradoxical that whereas GRK5 activity is antiatherogenic, β-arrestin2 activity is proatherogenic.19 However, at least 2 possibilities may help reconcile these findings. First, GRK5-mediated receptor phosphorylation may promote the ...
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3. Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, GRK3 isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. There are seven types of GRKs, named GRK1 to GRK7. GRK3 (also known as beta-adrenergic receptor kinase 2) is widely expressed in many ...
Background: Migration of leukocytes towards sites of inflammation, such as atherosclerotic lesions, is guided through chemokines, which interact with G protein-coupled receptors (GPCR) on leukocytes. This process is controlled by phosphorylation of these receptors through GPCR kinases (GRK). GRKs dampen the response of the chemokine signaling and as such regulate the migration of leukocytes towards the lesion. Given the major role of CCR1, CCR2, and CCR5 in atherogenesis, we focussed on GRK2 in this study, and assessed the role of GRK2 deficiency in haematopoietic cells on the atherogenic response in LDLr−/− mice.. Methods & Results: A bone marrow transplant was performed to generate LDLr−/− chimeras with a partial GRK2 deficiency in the haematopoietic lineage. GRK2+/− chimeras developed smaller lesions compared with wild-type controls (WT 585.0 ± 56.4x103 μm2 vs GRK2+/− 403.0 ± 43.8x103 μm2; p=0.017). Moreover, lesions in the GRK2+/− mice also had a 78% reduction in necrotic ...
Combining with epinephrine or norepinephrine to initiate a change in cell activity via activation of a G protein, with pharmacological characteristics of beta-adrenergic receptors; the activity involves transmitting the signal to the Gs alpha subunit of a…
The beta 2 adrenergic receptor (beta 2AR) undergoes desensitization by a process involving its phosphorylation by both protein kinase A (PKA) and G protein-coupled receptor kinases (GRKs). The protein kinase A-anchoring protein AKAP79 influences beta 2AR phosphorylation by complexing PKA with the receptor at the membrane. Here we show that AKAP79 also regulates the ability of GRK2 to phosphorylate agonist-occupied receptors. In human embryonic kidney 293 cells, overexpression of AKAP79 enhances agonist-induced phosphorylation of both the beta 2AR and a mutant of the receptor that cannot be phosphorylated by PKA (beta 2AR/PKA-). Mutants of AKAP79 that do not bind PKA or target to the beta 2AR markedly inhibit phosphorylation of beta 2AR/PKA-. We show that PKA directly phosphorylates GRK2 on serine 685. This modification increases Gbeta gamma subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor. Abrogation of the ...
TY - JOUR. T1 - Agonist dose-dependent phosphorylation by protein kinase A and G protein-coupled receptor kinase regulates β2 adrenoceptor coupling to Gi proteins in cardiomyocytes. AU - Liu, Ruijie. AU - Ramani, Biswarathan. AU - Soto, Dagoberto. AU - De Arcangelis, Vania. AU - Xiang, Yang Kevin. PY - 2009/11/20. Y1 - 2009/11/20. N2 - Adrenoceptors receptors (ARs) play a pivotal role in regulating cardiovascular response to catecholamines during β2ARs, prototypical G protein-coupled receptors (GPCRs), expressed in animal hearts, display dual coupling to both Gs and Gi proteins to control the adenylyl cyclase-cAMP dependent protein kinase A (PKA) pathway to regulate contraction responses. Here, we showed that β2AR coupling to Gi proteins was agonist dose-dependent and occurred only at high concentrations in mouse cardiac myocytes. Both β2AR-induced PKA activity, measured by fluorescence resonance energy transfer (FRET) imaging, and the increase in myocyte contraction rate displayed ...
Fingerprint Dive into the research topics of Nuclear Translocation of Cardiac G Protein-Coupled Receptor Kinase 5 Downstream of Select Gq-Activating Hypertrophic Ligands Is a Calmodulin-Dependent Process. Together they form a unique fingerprint. ...
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7. Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, GRK7 isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. There are seven types of GRKs, named GRK1 to GRK7. GRK7, also called iodopsin kinase, belongs to the visual group of GRKs. It is primarily ...
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Transcript Variant: This variant (7) has multiple differences compared to variant 1. These differences result in a distinct 5 UTR, 3 UTR, and 3 coding region, and cause translation initiation from a downstream start codon. The encoded isoform (g) has a shorter N-terminus and a distinct and shorter C-terminus, compared to isoform a ...
Complete information for GRK4 gene (Protein Coding), G Protein-Coupled Receptor Kinase 4, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Antigen receptor-dependent (AgR-dependent) stimulation of the NF-κB transcription factor in lymphocytes is a required event during adaptive immune response, but dysregulated activation of this signaling pathway can lead to lymphoma. AgR stimulation promotes assembly of the CARMA1-BCL10-MALT1 complex, wherein MALT1 acts as (a) a scaffold to recruit components of the canonical NF-κB machinery and (b) a protease to cleave and inactivate specific substrates, including negative regulators of NF-κB. In multiple lymphoma subtypes, malignant B cells hijack AgR signaling pathways to promote their own growth and survival, and inhibiting MALT1 reduces the viability and growth of these tumors. As such, MALT1 has emerged as a potential pharmaceutical target. Here, we identified G protein-coupled receptor kinase 2 (GRK2) as a new MALT1-interacting protein. We demonstrated that GRK2 binds the death domain of MALT1 and inhibits MALT1 scaffolding and proteolytic activities. We found that lower GRK2 levels in ...
Current projects emphasize attempts to understand regulation of the receptors and their desensitization which occurs in response to persistent stimulation. We are isolating the enzymes and proteins involved in these processes and studying their mechanisms of action in isolated protein and cellular systems as well as in whole animals. Most important are special enzymes called G protein-coupled receptor kinases which phosphorylate the receptors and lead to their desensitization which occurs when they bind a second protein called barrestin. Most recently we have been developing lines of transgenic animals in which these various proteins are either overexpressed or knockedout by homologous recombination. These genetically altered animal lines are helping to shed new light on the ways in which receptors are regulated. They also have suggested several novel approaches to human therapeutics ...
Current projects emphasize attempts to understand regulation of the receptors and their desensitization which occurs in response to persistent stimulation. We are isolating the enzymes and proteins involved in these processes and studying their mechanisms of action in isolated protein and cellular systems as well as in whole animals. Most important are special enzymes called G protein-coupled receptor kinases which phosphorylate the receptors and lead to their desensitization which occurs when they bind a second protein called barrestin. Most recently we have been developing lines of transgenic animals in which these various proteins are either overexpressed or knockedout by homologous recombination. These genetically altered animal lines are helping to shed new light on the ways in which receptors are regulated. They also have suggested several novel approaches to human therapeutics ...
G protein-coupled receptor kinase 2 promotes high-level Hedgehog signaling by regulating the active state of Smo through kinase-dependent and kinase-independent mechanisms in Drosophila ...
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The metabotropic glutamate 1 (mGlu(1)) receptor in cerebellar Purkinje cells plays a key role in motor learning and motor coordination. Here we show that the G protein-coupled receptor kinases (GRK) 2 and 4, which are expressed in these cells, regulate the mGlu(1) receptor by at least in part different mechanisms. Using kinase-dead mutants in HEK293 cells, we found that GRK4, but not GRK2, needs the intact kinase activity to desensitize the mGlu(1) receptor, whereas GRK2, but not GRK4, can interact with and regulate directly the activated Galpha(q). In cells transfected with GRK4 and exposed to agonist, beta-arrestin was first recruited to plasma membranes, where it was co-localized with the mGlu(1) receptor, and then internalized in vesicles. The receptor was also internalized but in different vesicles. The expression of beta-arrestin V53D dominant negative mutant, which did not affect the mGlu(1) receptor internalization, reduced by 70-80% the stimulation of mitogen-activated protein (MAP) ...
Introduction]: Insulin resistance (IR) and obesity are major health problems and important risk factors for the development of non-alcoholic fatty liver disease, a disease spectrum that may include hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. G protein-coupled receptor kinase 2 (GRK2), first identified as a regulator of G protein-coupled receptors (GPCRs), has been described to play a relevant role in the development of IR and obesity in vivo. However, the effect of GRK2 in the development of NASH had not been addressed so far. Since the deletion of GRK2 prevents excessive body weight gain, we fed WT and GRK2 global hemizygous mice (GRK2+/-) with a methionine and choline-deficient diet (MCD), a well stablished model of NASH that is independent of fat mass accretion. [Results]: Even though the MCD diet induced similar metabolic alterations and a comparable elevation in plasma transaminase activity in WT and GRK2+/- mice, other negative effects of the MCD were ...
The family of G-protein-coupled receptors includes many well-studied members, such as the adrenergic and the muscarinic acetylcholine receptors. These receptors are regulated by multiple mechanisms that serve to adapt their expression and their function to a rapidly changing environment. One of the most intriguing and important regulatory mechanisms involves the phosphorylation of such receptors by a set of specific kinases, termed the G-protein-coupled receptor kinases (GRKs). This phosphorylation is followed by binding of specific arrestin proteins to the phosphorylated receptors, which uncouples the receptors from their G proteins and thus causes a loss of receptor function. Several isoforms of the GRKs and the arrestins are expressed in the heart. They may be involved in the loss of receptor function in response to drugs. Furthermore, increased expression of one of the GRKs, β-adrenergic receptor kinase-1, has been found in failing hearts, and its increased activity may contribute to the loss of β
G-Protein-Coupled Receptor Kinases: A family of serine-threonine kinases that are specific for G-PROTEIN-COUPLED RECEPTORS. They are regulatory proteins that play a role in G-protein-coupled receptor densensitization.
Many G protein-coupled receptors, including the PTH receptor, undergo agonist-induced homologous desensitization, which is thought to be exerted by the sequential action of GRKs and β-arrestins. A role for GRKs in the regulation of the PTH receptors already can be inferred from experiments showing that inhibitors of PKA or PKC only partially inhibit PTH receptor phosphorylation in intact cells (21). Indeed, our studies show time- and agonist-dependent phosphorylation of the PTH receptor by GRKs in isolated membranes as well as in intact cells. The three widely distributed GRKs (2, 13, 42) showed an order of efficacy GRK2,GRK3,GRK5. In the membrane assay a stoichiometry of phosphorylation between 1 and 2 mol phosphate/mol receptor was obtained, a value that is similar to the one obtained for the prototypical β2-adrenergic receptor in a similar membrane preparation (43), even though much higher values have been reported for purified reconstituted β2-adrenergic receptors (44). This finding ...
MGI protein superfamily detail pages represent the protein classification set for a homeomorphic superfamily from the Protein Information Resource SuperFamily (PIRSF) site.. Mouse superfamily members are shown with links to their corresponding HomoloGene Classes. Note that pseudogenes are included in PIRSF families but not in orthology sets used here. You can select a given mouse superfamily member and download (or forward to NCBI BLAST) FASTA formatted protein sequences of that mouse gene and its mouse, human and rat homologs, as defined in the corresponding HomoloGene Class. The numbers of mouse, human and rat genes in the HomoloGene Class are shown. You can also Select all mouse superfamily members to obtain their protein sequences and the protein sequences for all mouse, human and rat homologs of the mouse superfamily members.. The number of protein sequences returned does not always match the numbers of homologs shown, because the same protein sequence can be associated with multiple ...
SignaGen Laboratories, A Gene Delivery Company Providing Custom AAV Adenovirus Lentivirus Production Services & Manufacturing DNA/siRNA Transfection Reagents... Ad-GIT2 [SL100903] - Product Category: Human Adenovirus Type5 (dE1/E3) expressing G Protein-coupled Receptor Kinase Interactor 2 (GIT2) under a CMV promoter. Product Information Product Name: G Protein-coupled Receptor Kinase Interactor 2, pre-packaged adenovirus, ready to ship and ready to use format. Promoter: CMV Titer: 1E+10~1E+11 PFU/ml Storage Buffer: DMEM with 2.5% BSA, 2.5% glycerol Gene Information Gene Name: G
Looking for online definition of homologous desensitization in the Medical Dictionary? homologous desensitization explanation free. What is homologous desensitization? Meaning of homologous desensitization medical term. What does homologous desensitization mean?
GRK6 - GRK6 (untagged)-Kinase deficient mutant (K215M) of Human G protein-coupled receptor kinase 6 (GRK6), transcript variant 2 available for purchase from OriGene - Your Gene Company.
Next-day shipping cDNA ORF clones derived from GRK2 G protein-coupled receptor kinase 2 available at GenScript, starting from $99.00.
Desipramine-yohimbine combination treatment of refractory depression. Implications for the beta-adrenergic receptor hypothesis of antidepressant action ...
By contrast, specific inhibition of endogenous GRK2 by dominant-negative mutants robustly inhibited OTR phosphorylation and internalization as well as arrestin/OTR interactions ...
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A role of GRK2 in the regulation of blood pressure has been shown in animal models with partial germline deletion, universal GRK2 knockdown, and targeted overexpression or knockdown in vascular smooth muscle and endothelial cells.22, 33, 34, 35, 36 GRK2 plays an important role in the regulation of blood pressure.7 Germline deletion of Grk2 is lethal.37 GRK2 deficiency in global adult hemizygous mice (Grk2+/−) has no effect on basal blood pressure but increases the vasodilator response to acetylcholine or isoproterenol and protects against Ang II-induced hypertension and vascular remodeling that is partially caused by increased nitric oxide bioavailability.33 Cohn et al also found in mice that inhibition of vascular smooth muscle GRK2 by either overexpression of the C‐terminal portion of GRK2 or vascular smooth muscle-specific ablation of GRK2 protein expression has no effect on blood pressure.35 This method of GRK2 silencing also had no effect on the elevated blood pressure resulting from ...
This study was initiated by revealing that two phases of dose-dependent Aβ effects existed in cultured microglial cells. One phase involves Aβ, in the micromolar range, directly inducing microglial TNF-α release as demonstrated previously (Meda et al., 1995). In addition to this known effect produced directly by Aβ, we discovered that, in the subthreshold nanomolar range, soluble Aβ, although insufficient to directly induce TNF-α release, can potentiate, in a dose-dependent manner, TNF-α release induced by other microglial activators, preferentially those that do so via GPCRs. Microglia-mediated inflammation is an important component of AD pathology (McGeer and McGeer, 2001). We showed recently that the ultimate coagulation factor, thrombin, a serine protease with elevated levels in AD brains (Akiyama et al., 1992), can activate microglial cells (as demonstrated by TNF-α induction, inducible nitric oxide synthase, and CD40 upregulation, etc.) via activation of G-protein-coupled PARs (Suo ...
G protein-coupled receptor kinase 2 (GRK2) participates together with β-arrestins in the regulation of G protein-coupled receptor signaling, but emerging evidence suggests that GRK2 can interact with a growing number of proteins involved in signaling mediated by other membrane receptor families under various pathologic conditions. We tested the hypothesis that GRK2 may be an important contributor to vascular endothelial dysfunction in diabetes. Human umbilical venous endothelial cells (HUVECs) were exposed to high glucose and high insulin (HG/HI) to mimic insulin-resistant diabetic conditions. GRK2 expression and membrane translocation were up-regulated under HG/HI conditions. HG/HI did not modify activation of Akt or endothelial nitric-oxide synthase (eNOS), but GRK2 inhibitor or small interfering RNA (siRNA) resulted in an increase in Akt and eNOS activation in HUVECs exposed to HG/HI. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation was increased after exposure to HG/HI, which ...
Title:Application of BRET for Studying G Protein-Coupled Receptors. VOLUME: 14 ISSUE: 5. Author(s):Agnieszka A. Kaczor, Magdalena Makarska-Bialokoz, Jana Selent, Rocio A. de la Fuente, Maria Marti-Solano and Marian Castro. Affiliation:Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Lab, Faculty of Pharmacy with Division of Medical Analytics, Medical University of Lublin, 4A Chodzki St., PL-20093 Lublin, Poland.. Keywords:BRET, G protein-coupled receptors, G protein-coupled receptor dimers.. Abstract:G protein-coupled receptors (GPCRs) constitute one of the largest classes of cell surface receptors. GPCR biology has been a subject of widespread interest owing to the functional relevance of these receptors and their potential importance in the development of new drugs. At present, over 30% of all launched drugs target these receptors. GPCRs have been considered for a long time to function as monomeric entities and the idea of GPCR dimerization ...
Optimization of the pyrrolotriazine series of HER kinase inhibitors led to the identification of BMS-690514, which is highly potent in inhibiting all 3 HER kinases (EGFR, HER2, and HER4). BMS-690514 is, in addition, a potent inhibitor of the VEGF receptor family. Outside of these 2 receptor kinase families, only a small number of additional protein kinases were found to interact with BMS-690514, and none of these other kinases is known to have a role in regulating tumor cell proliferation. In cell assays measuring receptor kinase inhibition, BMS-690514 showed potency that was comparable to its potency in cell proliferation assays, an observation that further confirms its on-target mechanism of action. The potency of BMS-690514 in inhibiting tumor cell proliferation reflects the role of EGFR and HER2 in epithelial cancer. EGFR and HER2 gene amplification in lung, gastric, and breast tumor cells predispose them to inhibition by BMS-690514. In addition, non-small cell lung tumors with activating ...
G protein-coupled receptors (GPCRs) are known to initiate a plethora of signaling pathways in vitro. However, it is unclear which of these pathways are engaged to mediate physiological responses. Here, we examine the distinct roles of Gq/11-dependent signaling and receptor phosphorylation-dependent …
BioTek Pôsteres Científicos, 28-Oct-09, A Cost-Effective Workflow for High-Throughput Screening of G Protein-Coupled Receptors (GPCR)
Dr. Koch would like to eventually perform large human trials to specifically look at levels of GRK2 to see if they can predict responses to drugs such as beta-blockers or other treatments for heart failure. We want to see in our proposed clinical trial if GRK2 can be a biomarker that can predict response to various therapies, he says. In animal models, we ve shown that when we lower GRK2 levels, the animal does better. We think that if a drug lowers GRK2 levels, the patient should benefit ...
A ready-to-use reverse transfection format RNAi screening library targeting mouse GPCR genes. Just resuspend pre-dispensed siRNA, and add cells. Optimization plates available.
GRK2 antibody, Internal (adrenergic, beta, receptor kinase 1) for WB. Anti-GRK2 pAb (GTX89353) is tested in Human samples. 100% Ab-Assurance.
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Noah's Arks Rescue is a 501c3 not for profit organization that supplies emergency medical, surgical and rehabilitation to abused animals. We are not a shelter.  Our wish and lifelong hope is that our Society becomes educated in the ethical treatment of all animals and to stop the senseless killing of animals that have been tortured and abused.
Noah's Arks Rescue is a 501c3 not for profit organization that supplies emergency medical, surgical and rehabilitation to abused animals. We are not a shelter.  Our wish and lifelong hope is that our Society becomes educated in the ethical treatment of all animals and to stop the senseless killing of animals that have been tortured and abused.
This Histri was built automatically but not manually verified. As a consequence, the Histri can be incomplete or can contain errors ...
... has been shown to interact with Beta adrenergic receptor kinase and Src. GRCh38: Ensembl release 89: ENSG00000185527 - ... link c-Src and G-protein-coupled receptor kinase 2 in a signaling unit that regulates p42/p44 mitogen-activated protein kinase ... link c-Src and G-protein-coupled receptor kinase 2 in a signaling unit that regulates p42/p44 mitogen-activated protein kinase ... cyclic guanosine monophosphate phosphodiesterase is a novel intermediate regulating p42/p44 mitogen-activated protein kinase ...
G protein receptor kinases (GRK) of GRK2 subfamily (beta-adrenergic receptor kinases): GRK2 and GRK3. Spectrin/pleckstrin-like ... PH domains of beta-adrenergic receptor kinase and beta-spectrin to WD40/beta-transducin repeat containing regions of the beta- ... Non-receptor tyrosine kinases belonging to the Btk/Itk/Tec subfamily. Insulin receptor substrate 1 (IRS-1). Regulators of small ... Komolov KE, Benovic JL (January 2018). "G protein-coupled receptor kinases: Past, present and future". Cellular Signalling. 41 ...
Beta adrenergic receptor kinase pathway "PDB101: Molecule of the Month: G Proteins". RCSB: PDB-101. Retrieved 24 August 2020. ... Sodeman W, Sodeman T (2005). "Physiologic- and Adenylate Cyclase-Coupled Beta-Adrenergic Receptors". Sodeman's Pathologic ... Neve KA, Seamans JK, Trantham-Davidson H (August 2004). "Dopamine receptor signaling". Journal of Receptor and Signal ... The inactive or inhibitory form exists when the complex consists of alpha, beta, and gamma subunits, with GDP bound to the ...
"Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2". Cell. 129 (3): 511 ... increased beta adrenergic receptor numbers in lung and heart, diminished tachyphylaxis to β2-adrenergic receptor agonists, ...
2002). "Beta 2-adrenergic receptor stimulated, G protein-coupled receptor kinase 2 mediated, phosphorylation of ribosomal ...
... has been shown to interact with RIPK4, beta adrenergic receptor kinase, PDLIM5 and GNB2L1. Protein kinase C GRCh38: ... Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene. Protein kinase C (PKC) is a family of ... portion of a human gene for protein kinase C beta I/beta II". Nucleic Acids Research. 15 (17): 7179-80. doi:10.1093/nar/15.17. ... "Pleckstrin homology domain of G protein-coupled receptor kinase-2 binds to PKC and affects the activity of PKC kinase". World ...
2001). "beta 1-adrenergic receptor association with the synaptic scaffolding protein membrane-associated guanylate kinase ... Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 also known as membrane-associated guanylate kinase ... "Entrez Gene: MAGI2 membrane associated guanylate kinase, WW and PDZ domain containing 2". Wood, J D; Yuan J; Margolis R L; ... This encoded protein is characterized by two WW domains, a guanylate kinase-like domain, and multiple PDZ domains. It has ...
2002). "G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95". J. Biol. Chem. 277 ( ... These kinases are a family of signaling molecules expressed at various submembrane domains and contain the PDZ, SH3 and the ... Ying Z, Bingaman W, Najm IM (2004). "Increased numbers of coassembled PSD-95 to NMDA-receptor subunits NR2B and NR1 in human ... 2000). "Formation of a native-like beta-hairpin finger structure of a peptide from the extended PDZ domain of neuronal nitric ...
He discovered that beta-1 adrenergic receptors and their regulatory G protein-coupled receptor kinases are dysregulated in ... Altered expression of β-adrenergic receptor kinase and β1-adrenergic receptors in the failing human heart. Circulation 87, 454- ... that increased β1-adrenergic receptor levels and signaling cause long-term cardiac damage contributed to the use of beta- ... Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ (1990): β-Arrestin: a protein that regulates β-adrenergic receptor ...
"Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted ... or β2-adrenergic receptor (β2-AR) -/-, or angiotensin II type 1a receptor (AT1a) -/-, or β-adrenergic receptor kinase 1 ... Fajardo G, Zhao M, Urashima T, Farahani S, Hu DQ, Reddy S, Bernstein D (October 2013). "Deletion of the β2-adrenergic receptor ... Conversely crossing MLP-/- mice with β1-adrenergic receptor (β1-AR) -/- mice was lethal, while crossing MLP-/- mice with ...
1995). "Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2 ... 1996). "Effect of different G protein-coupled receptor kinases on phosphorylation and desensitization of the alpha1B-adrenergic ... "Acidic amino acids flanking phosphorylation sites in the M2 muscarinic receptor regulate receptor phosphorylation, ... Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein- ...
... has been shown to interact with: ARHGEF7, Beta adrenergic receptor kinase, GIT2, PCLO, PLCG1, PPFIA4 PTK2, and liprin- ... "beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase- ... "Entrez Gene: GIT1 G protein-coupled receptor kinase interactor 1". Zhang H, Webb DJ, Asmussen H, Horwitz AF (2003). "Synapse ... beta by the yeast substrate-trapping system". Proc. Natl. Acad. Sci. U.S.A. 98 (12): 6593-6598. doi:10.1073/pnas.041608698. PMC ...
... variant of the uncoupling protein gene and the Trp64Arg mutation of the beta 3-adrenergic receptor gene on weight gain in ... Active protein kinase A, in turn, phosphorylates triacylglycerol lipase, thereby activating it. The lipase converts ... Sympathetic nervous system terminals release Norepinephrine onto a Beta-3 adrenergic receptor on the plasma membrane. This ... Schleiff E, Shore GC, Goping IS (Mar 1997). "Human mitochondrial import receptor, Tom20p. Use of glutathione to reveal specific ...
... stabilizes GRK2 and also orients it in a way that allows for more efficient phosphorylation of the beta adrenergic receptor, a ... PIP2 has been shown to recruit G protein-coupled receptor kinase 2 (GRK2) to the membrane by binding to the large lobe of GRK2 ... a membrane-bound enzyme activated through protein receptors such as α1 adrenergic receptors. PIP2 regulates the function of ... "Effect of Lipid Composition on Membrane Orientation of the G protein-coupled Receptor Kinase 2-Gβ1γ2 Complex". Biochemistry. 55 ...
... has been shown to interact with: Beta adrenergic receptor kinase, Bruton's tyrosine kinase, RGS16, RGS4 RIC8A, and Sodium- ... 7-transmembrane domain receptors to intracellular signaling pathways. Receptor activation catalyzes the exchange of GDP for GTP ... Petit A, Geoffroy P, Bélisle S (1997). "Expression of angiotensin II type-I receptor and phospholipase C-linked G alpha q/11 ... Laugwitz KL, Allgeier A, Offermanns S, Spicher K, Van Sande J, Dumont JE, Schultz G (1996). "The human thyrotropin receptor: a ...
The type 9 adenylyl cyclase is a widely distributed adenylyl cyclase, and it is stimulated by beta-adrenergic receptor ... It is regulated by a family of G protein-coupled receptors, protein kinases, and calcium. ... 2004). "An Ile to Met polymorphism in the catalytic domain of adenylyl cyclase type 9 confers reduced beta2-adrenergic receptor ... 1999). "Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 ...
2000). "Assembly of an A kinase-anchoring protein-beta(2)-adrenergic receptor complex facilitates receptor phosphorylation and ... receptors by cAMP-dependent protein kinase via selective interaction with receptor beta subunits". Mol. Cell. Neurosci. 22 (1 ... A-kinase anchor protein 5 is a protein that in humans is encoded by the AKAP5 gene. The A-kinase anchor proteins (AKAPs) are a ... The encoded protein binds to the RII-beta regulatory subunit of PKA, and also to protein kinase C and the phosphatase ...
Beta adrenergic receptor kinase, an intracellular enzyme Bark scale, an auditory frequency metric Bark or barque, a type of ...
... beta-adrenergic receptor kinase MeSH D12.776.476.250.067.249 - cdc2 protein kinase MeSH D12.776.476.250.067.500 - cdc28 protein ... casein kinase ialpha MeSH D12.776.476.150.300.200 - casein kinase idelta MeSH D12.776.476.150.300.300 - casein kinase iepsilon ... cyclin-dependent kinase 5 MeSH D12.776.476.250.067.900 - cyclin-dependent kinase 9 MeSH D12.776.476.250.580.500 - cdc2 protein ... tnf receptor-associated factor 1 MeSH D12.776.476.024.500.750 - tnf receptor-associated factor 2 MeSH D12.776.476.024.500.875 ...
... beta-adrenergic receptor kinase MeSH D12.644.360.200.150 - cyclic gmp-dependent protein kinases MeSH D12.644.360.200.575 - ... map kinase kinase kinase 1 MeSH D12.644.360.400.200 - map kinase kinase kinase 2 MeSH D12.644.360.400.300 - map kinase kinase ... kinase 3 MeSH D12.644.360.400.400 - map kinase kinase kinase 4 MeSH D12.644.360.400.500 - map kinase kinase kinase 5 MeSH ... map kinase kinase 1 MeSH D12.644.360.440.200 - map kinase kinase 2 MeSH D12.644.360.440.300 - map kinase kinase 3 MeSH D12.644. ...
... beta-adrenergic-receptor kinase MeSH D08.811.913.696.620.682.700.150.150 - cyclic gmp-dependent protein kinases MeSH D08.811. ... map kinase kinase kinase 1 MeSH D08.811.913.696.620.682.700.559.200 - map kinase kinase kinase 2 MeSH D08.811.913.696.620.682. ... map kinase kinase kinase 3 MeSH D08.811.913.696.620.682.700.559.400 - map kinase kinase kinase 4 MeSH D08.811.913.696.620.682. ... i-kappa B kinase MeSH D08.811.913.696.620.682.700.559 - map kinase kinase kinases MeSH D08.811.913.696.620.682.700.559.100 - ...
Beta adrenergic receptor kinase (βARK), a cytoplasmic kinase is activated and phosphorylates the C-terminus of the β2 receptor ... ßARK-phosphorylated receptors rather than protein kinase A-phosphorylated receptors, which suggests that the arrestins ... The ß2 adrenergic receptor was the first to have its desensitization studied and characterized. The mechanism of ... It has been shown to have no effect on adrenergic receptors (specifically ß2 and α1). "homologous desensitization". Medical ...
Protein kinase A phosphorylates and partially activates phosphorylase kinase. Adrenaline also binds to α1 adrenergic receptors ... acting through both alpha and beta adrenergic receptors to stimulate glycogenolysis. Adrenaline binds to β2 receptors on liver ... Sympathetic nerve receptors are classified as adrenergic, based on their responsiveness to adrenaline. The term "adrenergic" is ... Adrenaline's binding to these receptors triggers a number of metabolic changes. Binding to α-adrenergic receptors inhibits ...
Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2 There is no α1C receptor. There was a subtype known as C, but ... and β-Adrenergic Receptors Theory of receptor activation Desensitization of β1 receptors. ... Nisoli E, Tonello C, Landi M, Carruba MO (1996). "Functional studies of the first selective beta 3-adrenergic receptor ... Sep 2010). "Ghrelin secretion stimulated by {beta}1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice". ...
... beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes". Genomics. 23 (1): 286-8. doi:10.1006/geno. ... Arrestin beta 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. It is expressed at high ... Lefkowitz RJ (July 1998). "G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor ... "Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin". Science. 294 (5545): ...
... is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated ... Lefkowitz RJ (1998). "G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling ... 1999). "Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes". Science. 283 (5402): 655- ... 1990). "beta-Arrestin: a protein that regulates beta-adrenergic receptor function". Science. 248 (4962): 1547-50. doi:10.1126/ ...
... cAMP-dependent protein kinase-anchoring protein 250) binds the beta 2-adrenergic receptor via the receptor cytoplasmic Arg-329 ... binds the beta 2-adrenergic receptor via the receptor cytoplasmic Arg-329 to Leu-413 domain and provides a mobile scaffold ... Shih M, Lin F, Scott JD, Wang HY, Malbon CC (Jan 1999). "Dynamic complexes of beta2-adrenergic receptors with protein kinases ... Shih M, Lin F, Scott JD, Wang HY, Malbon CC (1999). "Dynamic complexes of beta2-adrenergic receptors with protein kinases and ...
"Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors". ... "Targeted beta-adrenergic receptor kinase (betaARK1) inhibition by gene transfer in failing human hearts". Circulation. 109 (13 ... "Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted ... "Cellular expression of the carboxyl terminus of a G protein-coupled receptor kinase attenuates G beta gamma-mediated signaling ...
"Protein kinase A-mediated phosphorylation of the beta 2-adrenergic receptor regulates its coupling to Gs and Gi. Demonstration ... Other adrenergic receptors Alpha-1 adrenergic receptor Alpha-2 adrenergic receptor Beta-1 adrenergic receptor Beta-3 adrenergic ... The beta-2 adrenergic receptor (β2 adrenoreceptor), also known as ADRB2, is a cell membrane-spanning beta-adrenergic receptor ... "Insulin stimulates sequestration of beta-adrenergic receptors and enhanced association of beta-adrenergic receptors with Grb2 ...
"Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation". J. Biol. Chem. 275 ... Other adrenergic receptors Alpha-1 adrenergic receptor Alpha-2 adrenergic receptor Beta-1 adrenergic receptor Beta-2 adrenergic ... The beta-3 adrenergic receptor (β3-adrenoceptor), also known as ADRB3, is a beta-adrenergic receptor, and also denotes the ... "Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation". J. Biol. Chem. 275 ...
amyloid-beta binding. • signal transducer activity. • Wnt-protein binding. • protein binding. • protein kinase binding. • ... transmembrane signaling receptor activity. • Wnt-activated receptor activity. • G-protein coupled receptor activity. ... "Frizzled Receptors: FZD5". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.. *v ...
Beta adrenergic receptor kinase (EC *Beta adrenergic receptor kinase. *Beta adrenergic receptor kinase-2 ... Receptor protein serine/threonine kinase (EC *Bone morphogenetic protein receptors *BMPR1 ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... Dephospho-(reductase kinase) kinase (EC *AMP-activated protein kinase α *PRKAA1 ...
Receptors. Varies greatly across species;. Human receptors: hTAAR1[2] and hTAAR2[2]. ... it reduces neuron firing rate and triggers protein kinase A (PKA) and protein kinase C (PKC) signaling, resulting in DAT ... or by cross-coupling with beta-amino organozinc reagents, or reacting a brominated arene with beta-aminoethyl organolithium ... Leffler, Esther B.; Spencer, Hugh M.; Burger, Alfred (1951). "Dissociation Constants of Adrenergic Amines". Journal of the ...
Re dhe vetëm beta receptor antagonist adrenergic, dichloroisoproterenol, gjithashtu ishte e pershkruara me larte dhe do të ... Unë pastaj u bë i interesuar në agjentë që mund të bllokojnë efektet e AMP ciklike në phosphorylase kinase dhe aktivizimin ... Alquist kishte raportuar më parë se efektet adrenergic mund të klasifikohen si alfa ose beta varësi të potencë relative të ... për shkak të efekteve beta adrenergic siç tregohet nga potencies relative e-isoproterenol l,-l epinephrine dhe-l norepinephrina ...
... β-adrenergic receptors. Lipid rafts that have been implicated in cell signaling events in nonerythroid cells have been shown in ... Excessive eryptosis is observed in red blood cells lacking the cGMP-dependent protein kinase type I or the AMP-activated ... beta-thalassemia, glucose-6-phosphate dehydrogenase deficiency, phosphate depletion, iron deficiency and Wilson's disease. ... as signaling receptors, as well as other currently unknown functions. The blood types of humans are due to variations in ...
May also modulate NMDA receptors and protein kinase C.. PO.. Half-life = 5-7 hours.. Neuropathic pain; epilepsy.. Fatigue, ... "Combining opioid and adrenergic mechanisms for chronic pain". Postgraduate Medicine. 126 (4): 98-114. doi:10.3810/pgm.2014.07. ... Beta blockers. *Calcium channel blockers. *renin-angiotensin system *ACE inhibitors. *Angiotensin II receptor antagonists ... Partial agonist at the mu opioid receptor; agonist at delta opioid receptor; antagonist at kappa opioid receptor.. Sublingual, ...
... (GAL1) is a G-protein coupled receptor encoded by the GALR1 gene.[5] ... "Galanin Receptors: GAL1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology ... This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it. *v ... galanin receptor activity. • protein binding. Cellular component. • integral component of membrane. • membrane. • plasma ...
... elevates the intracellular cAMP concentration via beta-adrenergic receptors and activates the cAMP-dependent protein kinase A ( ... In vertebrates, melatonin secretion is regulated by activation of the beta-1 adrenergic receptor by norepinephrine.[60] ... "Melatonin receptors , G protein-coupled receptors , IUPHAR/BPS Guide to Pharmacology". www.guidetopharmacology.org. Retrieved 7 ... In humans, melatonin is a full agonist of melatonin receptor 1 (picomolar binding affinity) and melatonin receptor 2 (nanomolar ...
Examples include beta adrenergic stimulation, stimulation of the glucagon receptor and ACTH stimulation of the ACTH receptor in ... protein kinase binding. • serine hydrolase activity. Cellular component. • cytoplasm. • membrane. • lipid droplet. • plasma ... Also, it may be activated by a cAMP-dependent protein kinase (PKA). This pathway is significantly less effective than the first ... 2002). "Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signal-regulated kinase pathway". J. Biol. ...
protein kinase C binding. • complement component C1q binding. • adrenergic receptor binding. • translation activator activity. ... 2001). "Interaction between GABA(A) receptor beta subunits and the multifunctional protein gC1q-R". J. Biol. Chem. 276 (28): ... C1QBP has been shown to interact with Protein kinase D1,[10] BAT2,[11] PRKCD,[10] PKC alpha[10] and Protein kinase Mζ.[10] ... 2000). "Protein kinase C [micro] is regulated by the multifunctional chaperon protein p32". J. Biol. Chem. 275 (32): 24601-7. ...
Bcr-Abl tyrosine-kinase inhibitors. *Cannabinoid receptor antagonists. *CCR5 receptor antagonists. *Neurokinin 1 receptor ... on beta blockers and cimetidine, and the discovery of statins by Akira Endo.[15] Another champion of the approach of developing ... who pioneered the first inhaled selective beta2-adrenergic agonist for asthma, the first inhaled steroid for asthma, ranitidine ... if the target is a protein kinase, the chemicals will be tested for their ability to inhibit that kinase.[citation needed] ...
Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors". Research Communications in ... regulated by Pyruvate dehydrogenase kinase and Pyruvate dehydrogenase phosphatase). to α-ketoglutaric acid. *Glutamate ... Inhibition by statins and beta blockers[edit]. CoQ10 shares a biosynthetic pathway with cholesterol. The synthesis of an ... intermediary precursor of CoQ10, mevalonate, is inhibited by some beta blockers, blood pressure-lowering medication,[10] and ...
stimulates AC, raises cAMP, stimulates beta catenin and Glycogen synthase kinase 3 ... Prostaglandin receptors or prostanoid receptors represent a sub-class of cell surface membrane receptors that are regarded as ... All of the prostanoid receptors are G protein-coupled receptors belonging to the Subfamily A14 of the rhodopsin-like receptor ... There are 9 established prostanoid receptors. The following table gives these receptors: a) full name; b) shortened names; c) ...
... but through its high affinity for alpha1 adrenergic receptors. It also has high affinity for H1 histaminergic receptors equal ... Rho kinase, and ERK pathway activation initiated by agonist stimulation of the receptor.[citation needed] ... "Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo". Proceedings of the ... The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G ...
for developing agents which block beta adrenergic and histamine receptors.. 1983/4 Не присуждалась ... for the discovery of protein kinases that phosphorylate tyrosine residues in proteins, critical for the regulation of a wide ... for his discovery of the gene super-family encoding nuclear receptors and elucidating the mechanism of action of this class of ... for major contributions to the understanding of the key antigen-specific molecules, the T cell receptor for antigen and ...
Beta adrenergic receptor kinase (EC *Beta adrenergic receptor kinase. *Beta adrenergic receptor kinase-2 ... Receptor protein serine/threonine kinase (EC *Bone morphogenetic protein receptors *BMPR1 ... Dephospho-(reductase kinase) kinase (EC *AMP-activated protein kinase α *PRKAA1 ... Myosin-heavy-chain kinase (EC *Aurora kinase *Aurora A kinase ...
epinephrine → β-adrenergic receptor. *produce glucose *stimulate glycogenolysis *phosphorylate glycogen phosphorylase via ... and beta-phosphate groups. The hydroxyl group the peptide substrate's Serine/Threonine attacks the gamma phosphate group at the ... out of 540 different protein kinase genes that make up for human kinome, only one other protein kinase, Casein kinase 2, is ... "cAMP-dependent protein kinase" redirects here. It is not to be confused with AMP-activated protein kinase or cyclin-dependent ...
Crystal structure of activated beta-2 adrenergic receptor in complex with Gs(PDB entry 3SN6). The receptor is colored red, Gα ... these activated kinases phosphorylate the receptor. The longer the receptor remains active the more kinases are activated and ... transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors ( ... "The interaction of beta-arrestin with the AP-2 adaptor is required for the clustering of beta 2-adrenergic receptor into ...
Dopamine receptors can also transactivate Receptor tyrosine kinases.[17] Beta Arrestin recruitment is mediated by G-protein ... μ-opioid receptors. ↑μ-opioid receptors. ↑κ-opioid receptors. ↑μ-opioid receptors. ↑μ-opioid receptors. No change. No change. [ ... D2 receptor signaling may mediate protein kinase B, arrestin beta 2, and GSK-3 activity, and inhibition of these proteins ... The D1 and D5 receptors are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 receptors are ...
... include the muscle-specific receptor tyrosine kinase (MuSK), the neuronal-specific kinase (NSK2), and ROR1 and ROR2. The ... "Frizzled Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.. ... Nusse R, Xu YK (1998). "The Frizzled CRD domain is conserved in diverse proteins including several receptor tyrosine kinases". ... Frizzled is a family of G protein-coupled receptor proteins[2] that serves as receptors in the Wnt signaling pathway and other ...
... activated DP2 also mobilizes G protein-coupled receptor kinases (GRKs, GRK2, GRK3, and/or GRK6) and Arrestin-2 (also termed ... G beta-gamma complex of subunits (Gβγ) have many potential functions, including simulation of phospholipase C to cleave ... with the C5a receptor, Formyl peptide receptor 1, and Formyl peptide receptor 2 receptors. DP2 has little or no such amino acid ... prostaglandin D receptor activity. • G-protein coupled receptor activity. • prostaglandin J receptor activity. • prostaglandin ...
"Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation". J. Biol. Chem. ( ... Beta-3 adrenergički receptor,[19] Kinaza beta adrenergičkog receptora,[8] Receptor epidermalnog faktora rasta,[9][20][21] PTK2, ... a receptor for activated C kinase and a homolog of the beta subunit of G proteins, inhibits activity of src tyrosine kinases ... Aryl hydrocarbon receptor,[7] PDE6G,[8] STAT1,[9][10] EPH receptor B2,[11][12] Androgenski receptor,[13][14][15] Proteinska ...
"A β2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2". Science. 293 (5527): 98-101. doi:10.1126/ ... In humans, cAMP works by activating protein kinase A (PKA, cAMP-dependent protein kinase), one of the first few kinases ... which results in the Gs alpha subunit's exchanging GDP for GTP and separation from the beta and gamma subunits. The Gs alpha ... an enzyme called protein kinase A (PKA).[12]. The PKA enzyme is also known as cAMP-dependent enzyme because it gets activated ...
The N-terminal signal peptides of corticotropin-releasing hormone receptor 1 and CRHR2 beta are cleaved off in the endoplasmic ... "Corticotropin-releasing Factor Receptors: CRF2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic ... corticotrophin-releasing factor receptor activity. • transmembrane signaling receptor activity. • peptide hormone binding. • ... CRF2 receptors are type 2 G protein-coupled receptors for corticotropin-releasing hormone (CRH) that are resident in the plasma ...
... determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes after receptor ... cell division is necessary for permanent neurotensin cell sensitization and leads to chronic mitogen-activated protein kinase ... "Neurotensin Receptors: NTS1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Neurotensin receptor 1, also called NTR1, belongs to the large superfamily of G-protein coupled receptors and is considered a ...
Lefkowitz, R.J. (1998). G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor ... "G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels". Biophys. J. 79 (5): 2547-56. ... Biogeno aminski receptor - Eikozanoidni receptor (Prostaglandinski receptor) - G protein-spregnuti receptor - Imunski receptor ... Neurotransmiterski receptor - Mirisni receptori - Proteazom-aktivirani receptor - Purinski receptor - Transferinski receptor ...
receptor serine/threonine kinase binding. • peroxisome proliferator activated receptor binding. • ubiquitin binding. ... and degradation of the beta2-adrenergic receptor". The Journal of Biological Chemistry. 283 (32): 22166-76. doi:10.1074/jbc. ... "Beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2". The Journal of Biological ... "Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ...
... has been found to bind with high to moderate affinity to the receptors alpha-1 and alpha-2 adrenergic, 5-HT7- and 5- ... "The G protein-coupled 5-HT1A receptor causes suppression of caspase-3 through MAPK and protein kinase Calpha". Biochimica et ... Beta blockers (e.g., alprenolol, carteolol, cyanopindolol, iodocyanopindolol, isamoltane, oxprenolol, penbutolol, pindobind, ... Repinotan acts as a selective high-affinity full receptor agonist at the 5-HT1A receptor subtype.[12] It increases the activity ...
Beta adrenergic receptor kinase (EC *Beta adrenergic receptor kinase. *Beta adrenergic receptor kinase-2 ... kinase activity. • protein binding. • ATP binding. • protein serine/threonine kinase activity. • protein kinase activity. ... Receptor protein serine/threonine kinase (EC *Bone morphogenetic protein receptors *BMPR1 ... Dephospho-(reductase kinase) kinase (EC *AMP-activated protein kinase α *PRKAA1 ...
... protein kinase A (PKA),[9] protein kinase B (PKB), also known as AKT[9]), and AMP Activated Protein Kinase (AMPK) cascades.[9] ... negative regulation of interleukin-1 beta production. • negative regulation of insulin secretion. • regulation of synapse ... dopamine receptor type 2 (DRD2),[11] melanocortin-3 receptor (MC3R), and serotonin receptor type 2C (5-HT2c receptor).[11] See ... Growth hormone secretagogue receptor(GHS-R), also known as ghrelin receptor, is a G protein-coupled receptor that binds growth ...
Beta adrenergic receptor kinase carboxyl-terminus (also βARKct) is a peptide composed of the last 194 amino acid residues of ... the carboxyl-terminus of beta adrenergic receptor kinase 1 (βARK1). It binds the βγ subunits of G proteins located in the ... "In Vivo Ventricular Gene Delivery of a β-Adrenergic Receptor Kinase Inhibitor to the Failing Heart Reverses Cardiac Dysfunction ... White DC, Hata JA, Shah AS, Glower DD, Lefkowitz RJ, Koch WJ (May 2000). "Preservation of myocardial β-adrenergic receptor ...
... kinase, beta-adrenergic receptor-specific kinase, beta-AR kinase, beta-ARK, beta-ARK 1, beta-ARK 2, beta-receptor kinase, GRK2 ... beta-adrenoceptor kinase, beta-adrenoceptor kinase 1, beta-adrenoceptor kinase 2, ADRBK1, BARK1, adrenergic receptor kinase, ... Other names in common use include ATP:beta-adrenergic-receptor phosphotransferase, [beta-adrenergic-receptor] ... a beta-adrenergic-receptor kinase (EC is an enzyme that catalyzes the chemical reaction: ATP + [beta-adrenergic ...
We now document that subtype 2 of the beta-adrenergic receptor kinase (beta ARK) is also involved in this process. By using ... A beta-adrenergic receptor kinase-like enzyme is involved in olfactory signal termination.. S Schleicher, I Boekhoff, J Arriza ... A beta-adrenergic receptor kinase-like enzyme is involved in olfactory signal termination. ... A beta-adrenergic receptor kinase-like enzyme is involved in olfactory signal termination. ...
... as well as the conditions favoring enhancement of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) by ... phosphorylation, we studied the effects of kinase activation and inhibition in hippocampal neurons. Inhibition of c … ... To identify the protein kinases regulating synaptic NMDA receptors, ... Beta-adrenergic regulation of synaptic NMDA receptors by cAMP-dependent protein kinase Neuron. 1996 Feb;16(2):415-21. doi: ...
Beta-adrenergic receptor kinase 1Imported. ,p>Information which has been imported from another database using automatic ... tr,F6Y9P3,F6Y9P3_MOUSE Beta-adrenergic receptor kinase 1 (Fragment) OS=Mus musculus GN=Grk2 PE=1 SV=1 ...
Compare and order Adrenergic, Beta, Receptor Kinase 1 ELISA Kits. View citations, images, detection ranges, sensitivity, prices ... beta-adrenergic receptor kinase 1 , adrenergic, beta, receptor kinase 1 , G-protein-coupled receptor kinase 2 , beta ARK , beta ... beta-adrenergic receptor kinase-1 , G-protein coupled receptor kinase 2 , adrenergic receptor kinase, beta 1 , beta-adrenergic ... Adrenergic, Beta, Receptor Kinase 1 ELISA Kit. 21 products by 10 suppliers: Abbexa , USBio , Assay Biotechnology , Wuhan Fine ...
The beta(2)-adrenergic receptor mediates extracellular signal-regulated kinase activation via assembly of a multi-receptor ... beta(2)-Adrenergic receptor (beta(2)AR) stimulation of COS-7 cells induces EGFR dimerization, tyrosine autophosphorylation, and ... beta(2)AR-mediated EGFR phosphorylation and subsequent beta(2)AR stimulation of extracellular signal-regulated kinase (ERK) 1/2 ... Many G protein-coupled receptors (GPCRs) activate MAP kinases by stimulating tyrosine kinase signaling cascades. In some ...
File:Beta adrenergic receptor kinase.JPG Beta Adrenergic Receptor Kinase Activation Pathway. ... "Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors". J ... "Desensitization of the isolated beta 2-adrenergic receptor by beta-adrenergic receptor kinase, cAMP-dependent protein kinase, ... Beta adrenergic receptor kinase (EC *Beta adrenergic receptor kinase. *Beta adrenergic receptor kinase-2 ...
Inhibition of beta-adrenergic receptor kinase prevents rapid homologous desensitization of beta 2-adrenergic receptors. Proc. ... G protein-coupled receptor kinases (GRKs) orchestrate biased agonism at the β2-adrenergic receptor ... G protein-coupled receptor kinases (GRKs) orchestrate biased agonism at the β2-adrenergic receptor ... G protein-coupled receptor kinases (GRKs) orchestrate biased agonism at the β2-adrenergic receptor ...
Human GRK2 in complex with human G-beta-gamma subunits and CCG211998 (14ak) ... Beta-adrenergic receptor kinase 1: A. Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1: B. Guanine nucleotide- ... Waldschmidt, H.V. et al., Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors ... Human GRK2 in complex with human G-beta-gamma subunits and CCG211998 (14ak). Coordinates. PDB Format Method. X-RAY DIFFRACTION ...
beta-adrenergic receptor kinase - A h i e ̃L i [ [ A ARK ... receptor editing Z v ^ [ ҏW receptor tyrosine kinase e ̌^ ` V L ... cyclin-dependent kinase inhibitor T C N ˑ L i [ [ C q r ^ [ ACKI ... phosphatidylinositol-3-kinase z X t @ ` W C m V g [ 3 L i [ [ API3K ... cyclin-dependent kinase T C N ˑ L i [ [ ACdk ... thymidine kinase ` ~ W L i [ [ thyroid hormone receptor b B z Z ...
... but also acts as a scaffold protein in extracellular signal-regulated kinase (ERK) cascade. Thus, we have examined the role of ... beta-arrestin2 in the betaAR-mediated ERK signaling pathways. Isoprotereno … ... Beta-arrestin mediates desensitization and internalization of beta-adrenergic receptors (betaARs), ... Beta-arrestin mediates desensitization and internalization of beta-adrenergic receptors (betaARs), but also acts as a scaffold ...
beta-adrenergic receptor kinase activity IDA Inferred from Direct Assay. more info ... beta-adrenergic receptor kinase activity IMP Inferred from Mutant Phenotype. more info ... GRK6 G protein-coupled receptor kinase 6 [Homo sapiens] GRK6 G protein-coupled receptor kinase 6 [Homo sapiens]. Gene ID:2870 ... Title: c-Src, Insulin-Like Growth Factor I Receptor, G-Protein-Coupled Receptor Kinases and Focal Adhesion Kinase are Enriched ...
Beta-adrenergic receptor kinase 1. A. 640. Homo sapiens. Mutation(s): 0 Gene Names: ADRBK1, BARK, BARK1, GRK2. EC: ... Crystal structure of G protein-coupled receptor kinase 2 in complex with a a rationally designed paroxetine derivative. *DOI: ... Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2 ... Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2 ...
β-AR, beta adrenergic receptor; PGE2, prostaglandin E2; AC, adenylate cyclase; Gsα, activating G protein-coupled subunit; PKA, ... Antioxidant-induced nuclear translocation of CCAAT/enhancer-binding protein beta. A critical role for protein kinase A-mediated ... Conditional deletion of membrane-bound beta-adrenergic receptors in renin cells results in a significant decrease in renin ... The cAMP pathway is activated through the β-adrenergic receptor or the prostaglandin E2 receptor. Phosphorylated CREB enters ...
Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor ... Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor ... A contributing mechanism for this impairment may involve enhanced myocardial beta-adrenergic receptor kinase (betaARK1) ... BACKGROUND: Impaired myocardial beta-adrenergic receptor (betaAR) signaling, including desensitization and functional ...
G-protein-coupled receptor kinase specificity for beta-arrestin recruitment to the beta2-adrenergic receptor revealed by ... G-protein-coupled receptor kinase specificity for beta-arrestin recruitment to the beta2-adrenergic receptor revealed by ... Here we use the beta(2)-adrenergic receptor (beta(2)AR), the archetypal nonvisual heptahelical receptor, as a model to test ... This switches a receptor from G-protein activation to G-protein desensitization, receptor internalization, and beta-arrestin- ...
Calcium/Calmodulin-Dependent Protein Kinase II Regulation of the Slow Delayed Rectifier Potassium Current, IKs, During ... During Sustained Beta-Adrenergic Receptor Stimulation. ... mediated primarily through β-adrenergic receptor (β-AR) ... HF has been demonstrated to increase the expression and function of calcium/calmodulin-dependent protein kinase II (CaMKII), a ... Calcium/Calmodulin-Dependent Protein Kinase II Regulation of the Slow Delayed Rectifier Potassium Current, IKs, ...
Regulation of beta-adrenergic receptors and αs. J Biol Chem 1989;264:10779-10786pmid:2471706. ... Coordinated phosphorylation of insulin receptor substrate-1 by glycogen synthase kinase-3 and protein kinase C betaII in the ... Specifically, given that inhibition of the β-adrenergic receptor blocks the sympathetic component of HRV, leaving the ... Given that inhibition of the β-adrenergic receptor blocks the sympathetic component of HRV, leaving the parasympathetic ...
... beta-adrenergic-receptor kinase [EC:] K00910 ADRBK; beta-adrenergic-receptor kinase [EC:] K04997 KCNJ3; ... 100762552 Grk2; G protein-coupled receptor kinase 2 100761290 Adrbk2; beta-adrenergic receptor kinase 2 100768536 Kcnj3; ... non-receptor tyrosine kinase 100766006 Prkca; protein kinase C alpha 100760922 Prkcb; protein kinase C beta 100762950 Prkcg; ... 100760922 Prkcb; protein kinase C beta 100762950 Prkcg; protein kinase C gamma 100769627 Grb2; growth factor receptor bound ...
G-protein-coupled receptor kinase specificity for beta-arrestin recruitment to the beta2-adrenergic receptor revealed by ... Selective increase of beta-adrenergic receptor kinase 1 and 2. J. Clin. Invest. 95:203-210. View this article via: JCI PubMed ... Different G protein-coupled receptor kinases govern G protein and beta-arrestin-mediated signaling of V2 vasopressin receptor. ... Functional antagonism of different G protein-coupled receptor kinases for beta-arrestin-mediated angiotensin II receptor ...
Human Beta-Amyloid Metabolic Process, Human Beta-Amyloid Binding, Human Beta-Adrenergic Receptor Kinase Activity ... Human Beta-Adrenergic Receptor Kinase Activity Human Beta-Adrenergic Receptor Kinase Activity: Polyclonal Antibody - PSD95 ... Human Beta-Adrenergic Receptor Activity Human Beta-Adrenergic Receptor Activity: Polyclonal Antibody - PSD95 Antibody, UniProt ... Human beta-2 Adrenergic Receptor Binding Human beta-2 Adrenergic Receptor Binding: Polyclonal Antibody - NEDD4 Antibody, ...
Beta-adrenergic receptor signaling in the heart: role of CaMKII. J Mol Cell Cardiol. 2010;48:322-330. doi: 10.1016/j.yjmcc. ... Sustained beta1-adrenergic stimulation modulates cardiac contractility by Ca2+/calmodulin kinase signaling pathway. Circ Res. ... ALDH2 indicates aldehyde dehydrogenase type 2; βAR, β-adrenergic receptor; LTCC, L-type calcium channel; MCU, mitochondria ... and ryanodine receptor 2 was detected in the postarrest period. Exogenous adrenergic activation in vivo recapitulated Ca2+ ...
2003) Protein kinase A and G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis ... 2000) Assembly of an A kinase-anchoring protein-beta(2)-adrenergic receptor complex facilitates receptor phosphorylation and ... 1999) Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science 283:655-661. ... Beta-adrenergic receptors (βARs) are members of the seven transmembrane receptor (7TMR) family that become activated upon ...
The beta-adrenergic receptor is a substrate for the insulin receptor tyrosine kinase. ... Phosphorylation of tyrosyl residues 350/354 of the beta-adrenergic receptor is obligatory for counterregulatory effects of ... Two different pathways link G-protein-coupled receptors with tyrosine kinases for the modulation of growth and survival in ... Regulation by insulin of phosphatidylinositol 3-kinase bound to alpha- and beta-isoforms of p85 regulatory subunit. ...
G Protein-Coupled Receptor Kinase 3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards ... Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the ... The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G ... ATP + [beta-adrenergic receptor] = ADP + [beta-adrenergic receptor] phosphate. *ARBK2_HUMAN,P35626 ...
One of the functions of GRK2 or beta-adrenergic kinase (ßARK1) is to turn off beta-adrenergic receptors. In heart failure, beta ... beta adrenergic receptor density is decreased, ßARK is increased and both together cause dysfunctional beta receptor signaling ... In congestive heart failure, the beta-adrenergic receptor system fails to work properly. Such receptors drive the heart both by ... GRK2 or beta-adrenergic kinase (ßARK1) is a Potential Biomarker for Heart Failure. Aug 20, 2005 - 4:55:00 PM ...
Protein Kinase A domains. β1AR-cAMP was unaffected by PMU in either microdomain. Consistent with this SICM/FRET analysis ... of the heart on the physiology of calcium and beta-adrenoceptor-cAMP (βAR-cAMP) microdomains. Previous studies have ... of the heart on the physiology of calcium and beta-adrenoceptor-cAMP (βAR-cAMP) microdomains. Previous studies have ... β(1,2)AR, beta-adrenergic receptor subtype 1 or 2; BAYK, BAYK8644; cAMP, cyclic adenosine monophosphate; CaMKII, calcium- ...
Adrenergic, beta, receptor kinase 1. NM_001619. Gene Info. AGAP3. ArfGAP with GTPase domain, ankyrin repeat and PH domain 3. NM ... Aryl hydrocarbon receptor interacting protein. NM_003977. Gene Info. AKAP1. A kinase (PRKA) anchor protein 1. NM_001242903. NM_ ... Activin A receptor, type I. NM_001105. NM_001111067. Gene Info. ACVRL1. Activin A receptor type II-like 1. NM_000020. NM_ ... Cyclin-dependent kinase 9. NM_001261. Gene Info. CDKN1B. Cyclin-dependent kinase inhibitor 1B (p27, Kip1). NM_004064. Gene Info ...
Adrenergic, beta, receptor kinase 2. NM_005160. Gene Info. AFAP1. Actin filament associated protein 1. NM_001134647. NM_198595 ... Adrenergic, beta, receptor kinase 1. NM_001619. Gene Info. ADRBK2. ... CDC42 binding protein kinase beta (DMPK-like). NM_006035. Gene Info. CDC42BPG. CDC42 binding protein kinase gamma (DMPK-like). ... Estrogen-related receptor beta. NM_004452. Gene Info. ESRRG. Estrogen-related receptor gamma. NM_001243509. NM_001243507. NM_ ...
  • Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2) that improves cardiac performance in live animals. (rcsb.org)
  • Next, we designed a benzolactam derivative of paroxetine that has optimized interactions with the hinge of the GRK2 kinase domain. (rcsb.org)
  • A team of scientists led by Walter Koch, Ph.D., director of the Center for Translational Medicine in the Department of Medicine in Jefferson Medical College of Thomas Jefferson University in Philadelphia, previously showed that an enzyme called GRK2 or beta-adrenergic kinase (ßARK1) is critically important in heart function. (rxpgnews.com)
  • Dr. Koch would like to eventually perform large human trials to specifically look at levels of GRK2 to see if they can predict responses to drugs such as beta-blockers or other treatments for heart failure. (rxpgnews.com)
  • One of the functions of GRK2 or beta-adrenergic kinase (ßARK1) is to turn off beta-adrenergic receptors. (rxpgnews.com)
  • Furthermore, pharmacological inhibition of G-protein receptor kinase 2 (GRK2), although not affecting the ability of [Met] 5 enkephalin to induce desensitization, acutely reversed the delay in recovery from desensitization produced by chronic morphine treatment. (jneurosci.org)
  • GRK2 activity is tightly controlled by different mechanisms including phosphorylation by kinases such as PKC, Src and ERK1 and 2, as well as interaction with various proteins. (thermofisher.com)
  • Pan troglodytes G protein-coupled receptor kinase 2 (GRK2), mRNA. (genscript.com)
  • Given the emerging role of signal transduction in these syndromes, we set out to explore the possible role that G protein-coupled receptor kinase 2 (GRK2), first identified as a G protein-coupled receptor regulator, could have as a modulator of insulin responses. (diabetesjournals.org)
  • RESEARCH DESIGN AND METHODS We analyzed the influence of GRK2 levels in insulin signaling in myoblasts and adipocytes with experimentally increased or silenced levels of GRK2, as well as in GRK2 hemizygous animals expressing 50% lower levels of this kinase in three different models of insulin resistance: tumor necrosis factor-α (TNF-α) infusion, aging, and high-fat diet (HFD). (diabetesjournals.org)
  • Title: G Protein-coupled Receptor Kinase 2 (GRK2) Promotes Breast Tumorigenesis Through a HDAC6-Pin1 Axis. (genscript.com)
  • G protein-coupled receptor kinase 2 (GRK2) plays a key role in the desensitization of G protein-coupled receptor signaling by phosphorylating activated heptahelical receptors and by sequestering heterotrimeric G proteins. (proteopedia.org)
  • In addition to phosphorylating the beta2-adrenergic receptor (beta2AR) and other receptors, G protein-coupled receptor kinase 2 (GRK2) can also phosphorylate tubulin, a nonreceptor substrate. (jove.com)
  • The closely related G protein-coupled receptor kinases GRK2 and GRK3 are both expressed in cardiac myocytes. (semanticscholar.org)
  • Although GRK2 has been extensively investigated in terms of regulation of cardiac beta-adrenergic receptors, the substrate specificities of the two GRK isoforms at G protein-coupled receptors (GPCR) are poorly understood. (semanticscholar.org)
  • The purpose of this study was to examine the expression levels of macrophage migration inhibitory factor (MIF) and G protein-coupled receptor kinase 2 (GRK2) in patients with early diabetic cardiomyopathy, and to investigate the mechanisms involved in MIF expression and GRK2 activation. (plos.org)
  • G-protein-coupled receptor kinase 2 (GRK2) is a member of a kinase family originally discovered for its role in the phosphorylation and desensitization of G-protein-coupled receptors. (genes2cognition.org)
  • We have previously shown that second-messenger-dependent kinases (cAMP-dependent kinase, protein kinase C) in the olfactory system are essential in terminating second-messenger signaling in response to odorants. (pnas.org)
  • steps 3 through 6) cAMP will then activate cAMP-dependent kinase ( PKA ), which, among other proteins that it acts on, will phosphorylate serine and threonine residues on βARK. (wikidoc.org)
  • Heparin, an inhibitor of beta ARK, as well as anti-beta ARK-2 antibodies, (i) completely prevents the rapid decline of second-messenger signals (desensitization) that follows odorant stimulation and (ii) strongly inhibits odorant-induced phosphorylation of olfactory ciliary proteins. (pnas.org)
  • Thus, stimulation of beta-adrenergic receptors during excitatory synaptic transmission can increase charge transfer and Ca2+ influx through NMDA receptors. (nih.gov)
  • Here we report that GPCR activation mimics growth factor-mediated stimulation of the epidermal growth factor receptor (EGFR) with respect to many facets of RTK function. (uniprot.org)
  • beta(2)-Adrenergic receptor (beta(2)AR) stimulation of COS-7 cells induces EGFR dimerization, tyrosine autophosphorylation, and EGFR internalization. (uniprot.org)
  • beta(2)AR-mediated EGFR phosphorylation and subsequent beta(2)AR stimulation of extracellular signal-regulated kinase (ERK) 1/2 are sensitive to selective inhibitors of both EGFR and Src kinases, indicating that both kinases are required for EGFR transactivation. (uniprot.org)
  • beta(2)AR-dependent signaling to ERK1/2, like direct EGF stimulation of ERK1/2 activity, is sensitive to inhibitors of clathrin-mediated endocytosis, suggesting that signaling downstream of both the EGF-activated and the GPCR-transactivated EGFRs requires a productive engagement of the complex with the cellular endocytic machinery. (uniprot.org)
  • steps 1) Upon stimulation of the Beta adrenergic receptor by epinephrine , Gs will be activated. (wikidoc.org)
  • Pertussis toxin treatment and blockade of Gbetagamma action inhibited beta-arrestin2-enhanced nuclear activation of ERK, suggesting that beta-arrestin2 promotes nuclear ERK localization in a Gbetagamma dependent mechanism upon receptor stimulation. (nih.gov)
  • Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor stimulation and blockade. (duke.edu)
  • CONCLUSIONS: This report demonstrates, for the first time, that betaAR stimulation can significantly increase the expression of betaARK1 , whereas beta-blockade decreases expression. (duke.edu)
  • Sustained elevations in catecholaminergic signaling, mediated primarily through β-adrenergic receptor (β-AR) stimulation, are a hallmark neurohormonal alteration in heart failure (HF) that contribute to pathophysiologic cardiac remodeling. (purdue.edu)
  • Parasympathetic modulation of heart rate is mediated by binding of acetylcholine (ACh) released in response to vagal stimulation to M 2 muscarinic receptors resulting in hyperpolarization of the myocyte membrane and prolonged diastolic depolarization through the ACh-activated inward-rectifying K + channels (I KACh ) located primarily in the atria. (diabetesjournals.org)
  • We show that in HEK293 cells, stimulation of mitogen-activated protein (MAP) kinase by the beta2-adrenergic receptor is mediated by the betagamma subunits of pertussis-toxin-sensitive G proteins through a pathway involving the non-receptor tyrosine kinase c-Src and the G protein Ras. (nih.gov)
  • The appreciation that chronic stimulation of βARs likely contributes to the pathogenesis of heart failure ( 4 ) has led to the use of β-adrenergic receptor antagonists (i.e., β-blockers) to competitively inhibit the harmful effects of chronic catecholamine stimulation ( 5 ). (pnas.org)
  • Stimulation of the β 2 -adrenergic receptor (β 2 AR) in human embryonic kidney (HEK) 293 cells causes a transient activation of Extracellular Signal-Regulated Kinase (ERK) 1/2. (aspetjournals.org)
  • Bbeta-adrenergic receptor kinase-1 levels in catecholamine-induced myocardial hypertrophy: regulation by beta- but not alpha1-adrenergic stimulation. (duke.edu)
  • The activated insulin receptor can phosphorylate the G protein subunit Gαq/11, leading to activation of cdc42 and PI3K, which triggers glucose transport stimulation ( 14 - 16 ). (diabetesjournals.org)
  • 2004) Characterization of agonist stimulation of cAMP‐dependent protein kinase and G protein‐coupled receptor kinase phosphorylation of the beta2‐adrenergic receptor using phosphoserine‐specific antibodies. (els.net)
  • Anton-Tay F, Ramirez G, Martinez I and Benitez-King G. In vitro stimulation of protein kinase C by melatonin. (angelfire.com)
  • Stimulation of I CaL by the catalytic subunit of the cAMP-dependent protein kinase A (PKA) was found to be similar (about 3 times) throughout development and in adult mouse ventricular cardiomyocytes, indicating that no structural changes of the Ca 2+ channel related to phosphorylation occurred during development. (ahajournals.org)
  • We conclude that uncoupling and/or low expression of G s protein accounted for the I CaL insensitivity to β-adrenergic stimulation in VEDS cardiomyocytes. (ahajournals.org)
  • An important process in regulating heart rate and excitation-contraction coupling by sympathetic nerves is the stimulation of the high-threshold (L-type) Ca 2+ current ( I CaL ) by β-adrenergic agonists. (ahajournals.org)
  • Synaptic stimulation of mTOR is mediated by Wnt signaling and regulation of glycogen synthetase kinase-3. (semanticscholar.org)
  • In the heart, cAMP, or agents that increase cAMP accumulation also do not alter basal production of PGI 2 but inhibit that elicited by stimulation of beta -AR with ISOP ( Williams and Malik, 1989 ). (aspetjournals.org)
  • For example, it may help to explain why stimulation of the beta-adrenergic receptors increases the mechanical performance of the failing heart in the short term yet is detrimental in the long term. (innovations-report.com)
  • Phosphorylation of GTP-binding-regulatory (G)-protein-coupled receptors by specific G-protein-coupled receptor kinases (GRKs) is a major mechanism responsible for agonist-mediated desensitization of signal transduction processes. (duke.edu)
  • Although cellular context controls the final output of a signaling pathway, most experiments suggest that the core components of each pathway - ligand, receptor, cytoplasmic signal transduction machinery and transcription factor - have been conserved in evolution. (biologists.org)
  • Phosphoinositide (PI) 3-kinases control essential cellular functions such as cytoskeletal dynamics, signal transduction and membrane trafficking. (biologists.org)
  • Extracellular signal-regulated kinases(ERKs), belonging to the family of mitogen-activated protein kinases (MAPKs), are cytoplasmic and nuclear serine/threonine kinases involved in the signal transduction of several extracellular effectors. (sun.ac.za)
  • Since H 2 O 2 and oxyradicals were found to produce biphasic changes in the β-adrenergic signal transduction mechanism, it is likely that the observed changes in the ischemic and ischemic-reperfused hearts may be due to the accumulation of low vs. high concentrations of oxyradicals and oxidants such as H 2 O 2 . (springer.com)
  • We showed that an alanine mutant of the highly conserved residue tyrosine 219 (Y219A) in transmembrane domain five of the β 2 -adrenergic receptor (β 2 AR) was incapable of β-arrestin recruitment, receptor internalization, and β-arrestin-mediated activation of extracellular signal-regulated kinase (ERK), whereas it retained the ability to signal through G protein. (sciencemag.org)
  • Beta-arrestin mediates desensitization and internalization of beta-adrenergic receptors (betaARs), but also acts as a scaffold protein in extracellular signal-regulated kinase (ERK) cascade. (nih.gov)
  • This switches a receptor from G-protein activation to G-protein desensitization, receptor internalization, and beta-arrestin-dependent signal activation. (duke.edu)
  • One of the mechanisms proposed for this activation is a PKA-mediated phosphorylation of the β 2 AR that switches receptor coupling from G s to G i and triggers internalization of the receptor. (aspetjournals.org)
  • Our results indicate that the dominant mechanism of β 2 AR activation of ERK1/2 does not require PKA phosphorylation of the β 2 AR, receptor internalization or switching from activation of G s to G i but clearly requires activation of a Src family member that may be downstream of PKA. (aspetjournals.org)
  • Internalization of the GPCRs ,regulated by beta-arrestin-1, leads to activation of the Ras - Raf - ERK1 and 2 signaling pathway. (thermofisher.com)
  • 5 , 6 Conversely, in cardiomyocytes, PI3Kγ negatively controls cAMP levels as a scaffold protein 7 , 8 and plays a pivotal role during the internalization of activated β-adrenergic receptors via its kinase activity. (ahajournals.org)
  • Internalization of VE-cadherin as well as c-Src kinase-dependent phosphorylation have been implicated in the loosening of cell-cell contacts, thereby modulating vascular permeability. (biologists.org)
  • Arrestin proteins then bind to the phosphorylated receptor initializing clathrin-mediated internalization. (ahajournals.org)
  • Biased signaling agonist of Dopamine D3 receptor induces receptor internalization independent of β-Arrestin recruitment. (bioportfolio.com)
  • Agonist-induced internalization of G protein-coupled receptors (GPCRs) is a significant step in receptor kinetics and is known to be involved in receptor down-regulation. (bioportfolio.com)
  • G-protein-coupled receptor kinase specificity for beta-arrestin recruitment to the beta2-adrenergic receptor revealed by fluorescence resonance energy transfer. (duke.edu)
  • Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A. (nih.gov)
  • For example, although most of the actions of the prototype beta2-adrenergic receptor are mediated through Gs proteins and the cyclic-AMP-dependent protein kinase (PKA) system, beta-adrenergic receptors can also couple to Gi proteins. (nih.gov)
  • Activation of this pathway by the beta2-adrenergic receptor requires that the receptor be phosphorylated by PKA because it is blocked by H-89, an inhibitor of PKA. (nih.gov)
  • Our results demonstrate that a mechanism previously shown to mediate uncoupling of the beta2-adrenergic receptor from Gs and thus heterologous desensitization (PKA-mediated receptor phosphorylation), also serves to 'switch' coupling of this receptor from Gs to Gi and initiate a new set of signalling events. (nih.gov)
  • Kallal L, Gagnon AW, Penn RB and Benovic JL (1998) Visualization of agonist‐induced sequestration and down‐regulation of a green fluorescent protein‐tagged beta2‐adrenergic receptor. (els.net)
  • Shenoy SK, McDonal PH, Kohout TA and Lefkowitz RJ (2001) Regulation of receptor fate by ubiquitination of activated beta2‐adrenergic receptor and beta‐arrestin. (els.net)
  • Shumay E, Gavi S, Wang HY and Malbon CC (2004) Trafficking of beta2‐adrenergic receptors: insulin and beta‐agonists regulate internalisation by distinct cytoskeletal pathways. (els.net)
  • Tao J, Wang HY and Malbon CC (2003) Protein kinase A regulates AKAP250 (gravin) scaffold binding to the beta2‐adrenergic receptor. (els.net)
  • 2005). "beta2-Adrenergic receptor gene variations associated with stage-2 hypertension in northern Han Chinese. (wikipedia.org)
  • Inhibition of cAMP-dependent protein kinase (PKA) prevented recovery of NMDA receptors from calcineurin-mediated dephosphorylation induced by synaptic activity, suggesting that tonically active PKA phosphorylates receptors during quiescent periods. (nih.gov)
  • The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating their deactivation. (nih.gov)
  • The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors. (genecards.org)
  • Beta-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. (duke.edu)
  • beta-Adrenergic receptor kinase (beta-AR kinase) is a cytosolic enzyme that phosphorylates the beta-adrenergic receptor only when it is occupied by an agonist [Benovic, J. Strasser, R. H., Caron, M. G. & Lefkowitz, R. J. (duke.edu)
  • The product of this gene phosphorylates the beta-2-adrenergic receptor and appears to mediate agonist-specific desensitization observed at high agonist concentrations. (thermofisher.com)
  • This protein is an ubiquitous cytosolic enzyme that specifically phosphorylates the activated form of the beta-adrenergic and related G-protein-coupled receptors. (thermofisher.com)
  • The encoded protein phosphorylates the beta-adrenergic receptor as well as a wide range of other substrates including non-GPCR cell surface receptors, and cytoskeletal, mitochondrial, and transcription factor proteins. (genscript.com)
  • In turn, activated p38 phosphorylates numerous substrates which include kinases such as MAPK-activated protein kinase 2 (MAPKAPK-2) and -3 ( 18 , 34 , 49 ). (asm.org)
  • To identify the protein kinases regulating synaptic NMDA receptors, as well as the conditions favoring enhancement of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) by phosphorylation, we studied the effects of kinase activation and inhibition in hippocampal neurons. (nih.gov)
  • However, there was an associated increase in the potency for inhibition of other AGC kinases, suggesting that the unconventional hydrogen bond formed by the benzodioxole ring of paroxetine is better accommodated by GRKs. (rcsb.org)
  • knocking out of the beta1/2 (zeige TFAP2B Antikörper ) receptor significantly diminished the ST25 acupuncture-induced inhibition of gastric motility and jejunal motility without significantly altering the enhancement of colonic motility induced by acupuncture at ST25. (antikoerper-online.de)
  • Inhibition of protein tyrosine kinases or protein kinase C has little effect on NMDAR currents potentiated by nerve injury. (aspetjournals.org)
  • Benitez-King G, Rios A, Martinez A and Anton-Tay F. In vitro inhibition of Ca2+/calmodulin-dependent kinase II activity by melatonin. (angelfire.com)
  • Due to the tetrameric composition of protein kinase A (PKA) of both, regulatory and catalytic subunits, inhibition of PKA can be achieved either by inhibitory analogues of cyclic AMP or by structures that block the ATP binding site (isoquinolines, staurosporine analogues). (biolog.de)
  • Counterregulation by growth factor receptor tyrosine kinases and homologous desensitization by GRKs share many similarities in receptor phosphorylation, use of accessory proteins and sequestration of the receptors. (els.net)
  • Counterregulation by growth factor receptor tyrosine kinases and homologous desensitization by GRKs both stimulate the sequestration of β2‐AR. (els.net)
  • Whereas subclass IA PI 3-kinases are typically activated by receptor tyrosine kinases (RTKs) or receptors for immunoglobulin G (FcγRs), subclass IB enzymes are activated by G-protein-coupled receptors (GPCRs). (biologists.org)
  • This enzyme belongs to the family of transferases, specifically those transferring a phosphate group to the sidechain oxygen atom of serine or threonine residues in proteins (protein-serine/threonine kinases). (wikipedia.org)
  • However, our knowledge of how receptors, cAMP signaling enzymes, effectors, and other key proteins form specific signaling complexes to regulate specific cell responses is limited. (aspetjournals.org)
  • A-kinase-anchoring proteins, of which there are 43 different isoforms, facilitate this by targeting protein kinase A to specific substrates. (aspetjournals.org)
  • The classic model of G protein-coupled receptor (GPCR) signaling, where receptors, G proteins, effector enzymes, and downstream signaling proteins float in a sea of phospholipids and interact with one another stochastically and generate a global signal via a second messenger, does not explain pharmacological reality. (aspetjournals.org)
  • After binding to their ligand and interacting with heterotrimeric G proteins, GPCRs (e.g., ?2-adrenergic receptor) are phosphorylated by GRKs. (thermofisher.com)
  • This gene encodes a member of the G protein-coupled receptor kinase family of proteins. (genscript.com)
  • G-Proteins form a link between the cell surface receptors and the intracellular events by interacting with GTP. (researchimpact.com)
  • These proteins are also known as 7 TM, seven trans-membranes or serpentine receptors because in all cases the signaling through heterotrimeric G-Proteins is not exhibited. (researchimpact.com)
  • Operating via heterotrimeric G proteins, adrenergic receptors constitute one of the most intensely studied classes of membrane proteins, whose expression and function are subject to regulation at many different levels, including transcriptional, posttranscriptional and posttranslational. (els.net)
  • The encoded proteins belong to the membrane-associated guanylate kinases (MAGUKs) and are collectively called MAGI family proteins. (springer.com)
  • Other MAGUKs, such as ZO-1, PSD-95, and CASK, harbor the guanylate kinase (GK) domain in the C-terminal region, while MAGI family proteins have the GK domain in the N-terminal region (Funke et al. (springer.com)
  • Stargazin and other transmembrane AMPA receptor regulating proteins interact with synaptic scaffolding protein MAGI-2 in brain. (springer.com)
  • A novel multiple PDZ domain-containing molecule interacting with N-methyl-D-aspartate receptors and neuronal cell adhesion proteins. (springer.com)
  • The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. (proteopedia.org)
  • Since cAMP was formerly believed to transmit signals through only two direct target molecules, protein kinase A and the cyclic nucleotide-gated channel, the sensational discovery in 1998 of another novel direct effecter of cAMP [exchange proteins directly activated by cAMP (Epac)] attracted a great deal of scientific interest in cAMP signaling. (springer.com)
  • FYVE, PX and PH domains mediate the binding of effector proteins to the lipid products of PI 3-kinases. (biologists.org)
  • The domains can bind phosphatidylinositol within biological membranes and proteins such as the beta/gamma subunits of heterotrimeric G proteins [ PMID: 8074669 ] and protein kinase C [ PMID: 7522330 ]. (ebi.ac.uk)
  • Cytoskeletal proteins such as dynamin (see IPR001401 ), Caenorhabditis elegans kinesin-like protein unc-104 (see IPR001752 ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1. (ebi.ac.uk)
  • The key enzyme in heart muscle signaling, PKA, is a member of a huge class of regulatory proteins called kinases. (innovations-report.com)
  • Each kinase is specialized to attach a phosphate molecule to a specific set of target proteins. (innovations-report.com)
  • The activity of kinases is delicately balance by a group of enzymes called protein phosphatases, which simply remove phosphate groups from specific proteins, inactivating them. (innovations-report.com)
  • About 30 percent of all human proteins are regulated by kinases and phosphatases. (innovations-report.com)
  • This protein belongs to a small subclass of adenylyl cyclase proteins that are functionally related and are inhibited by protein kinase A, calcium ions and nitric oxide. (genecards.org)
  • Traditionally, activated receptors couple to G proteins, which transduce downstream signals via second messengers and membrane channels. (ahajournals.org)
  • Arrestins not only scaffold proteins for the activation of different MAPK families under single receptor activation, but also mediate transactivation of epidermal growth factor receptor signaling pathways 2,6 and activation of many other non-GPCR signaling cascades. (ahajournals.org)
  • 7 In the case of GPCR-induced extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) activation, both G proteins and arrestins are capable of mediating ERK activation via independent mechanisms, with each pathway leading to unique spatiotemporal consequences. (ahajournals.org)
  • However, because GPCR kinase (GRK)-dependent receptor phosphorylation is a critical prerequisite for the recruitment of β-arrestins to most GPCRs, GRKs themselves may play an important role in establishing biased signaling. (sciencemag.org)
  • This market insight report on G-Protein Coupled Receptors (GPCR) covers the types of GPCR Families and the various ligands targeting GPCR. (researchimpact.com)
  • At present the development of drugs is centered on the discovery of chemicals that influence the ability of the ligands to bind with the G-Protein Coupled Receptor or GPCR. (researchimpact.com)
  • This chapter gives an insight into various types of GPCR Receptors and Ligands including definitions. (researchimpact.com)
  • We aimed to characterize the cellular mechanism by which GPCR crosstalk regulates mitogen-activated protein kinase (MAPK) activation. (ahajournals.org)
  • 1 Active GPCRs are phosphorylated by specific GPCR kinases (GRKs) leading to receptor desensitization. (ahajournals.org)
  • Myeloid-specific GPCR kinase-2 negatively regulates NF-κB1p105-ERK pathway and limits endotoxemic shock in mice. (genes2cognition.org)
  • Conversely, elevation of PKA activity by forskolin, cAMP analogs, or the beta-adrenergic receptor agonists norepinephrine and isoproterenol overcame the ability of calcineurin to depress the amplitude of NMDA EPSCs. (nih.gov)
  • Biased agonists of G protein-coupled receptors (GPCRs), which selectively activate either G protein- or β-arrestin-mediated signaling pathways, are of major therapeutic interest because they have the potential to show improved efficacy and specificity as drugs. (sciencemag.org)
  • With acute administration, morphine is unlike many other opioid agonists in that it does not mediate robust acute desensitization or induce receptor trafficking. (jneurosci.org)
  • Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus. (angelfire.com)
  • Exposure of G protein-coupled receptors (GPCRs) to agonists can desensitize receptor signaling and lead to drug tolerance, whereas, inverse agonists may sensitize signaling. (bioportfolio.com)
  • The small family of G-protein-coupled receptor kinases (GRKs) regulate cell signaling by phosphorylating heptahelical receptors, thereby promoting receptor interaction with beta-arrestins. (duke.edu)
  • However, the specificity of GRKs for recruiting beta-arrestins to specific receptors has not been elucidated. (duke.edu)
  • We show that beta(2)AR phosphorylation is required for high affinity beta-arrestin binding, and we use small interfering RNA silencing to show that HEK-293 and U2-OS cells use different subsets of their expressed GRKs to promote beta-arrestin recruitment, with significant GRK redundancy evident in both cell types. (duke.edu)
  • G protein-coupled receptor kinases (GRKs) are important regulators of G protein-coupled receptors(GPCRs). (thermofisher.com)
  • This reciprocal regulation of betaARK1 documents a novel mechanism of ligand-induced betaAR regulation and provides important insights into the potential mechanisms responsible for the effectiveness of beta-blockers, such as carvedilol, in the treatment of heart failure. (duke.edu)
  • Because GRK isoforms vary in their regulation, this partially redundant system ensures beta-arrestin recruitment while providing the opportunity for tissue-specific regulation of the rate of beta-arrestin recruitment. (duke.edu)
  • An approach to the study of G-protein-coupled receptor kinases: an in vitro-purified membrane assay reveals differential receptor specificity and regulation by G beta gamma subunits. (duke.edu)
  • Even though NM receptor regulation is implicated in the pharmacological action of many drugs, and is also known to be influenced by various environmental factors, its functional consequences and modes of action are not well understood. (cogprints.org)
  • In this paper we summarize relevant experimental evidence on NM receptor regulation (specifically dopamine D1 and D2 receptors) in order to explore its significance for neural and synaptic plasticity. (cogprints.org)
  • We identify the relevant components of NM receptor regulation (receptor phosphorylation, receptor trafficking and sensitization of second-messenger pathways) gained from studies on cultured cells. (cogprints.org)
  • Key principles in the regulation and control of short-term plasticity (sensitization) are identified, and a model is presented which employs direct and indirect feedback regulation of receptor efficacy. (cogprints.org)
  • Finally, we discuss the implications of NM receptor regulation for models of brain plasticity and memorization.We emphasize that a realistic model of brain plasticity will have to go beyond Hebbian models of long-term potentiation and depression to include plasticity in the distribution and efficacy of NM receptors. (cogprints.org)
  • Hadcock JR and Malbon CC (1988) Down‐regulation of beta‐adrenergic receptors: agonist‐induced reduction in receptor mRNA levels. (els.net)
  • Kohout TA and Lefkowitz RJ (2003) Regulation of G protein‐coupled receptor kinases and arrestins during receptor desensitization. (els.net)
  • Krupnick JG and Benovic JL (1998) The role of receptor kinases and receptors in G‐protein‐coupled receptor regulation. (els.net)
  • Role of TARP interaction in S-SCAM-mediated regulation of AMPA receptors. (springer.com)
  • Gannon, A.M. and Kinsella, B.T. (2008) Regulation of the Human Thromboxane A2 Receptor Gene by Sp1, Egr1, NF-E2, GATA-1, and Ets-1 in Megakaryocytes. (scirp.org)
  • Substrate specificities of g protein-coupled receptor kinase-2 and -3 at cardiac myocyte receptors provide basis for distinct roles in regulation of myocardial function. (semanticscholar.org)
  • Myocardial distribution and regulation of GRK and beta-arrestin isoforms in congestive heart failure in rats. (semanticscholar.org)
  • Among its related pathways are GABAergic synapse and Regulation of CFTR activity (norm and CF) . GO annotations related to this gene include protein kinase binding and adenylate cyclase activity . (genecards.org)
  • Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion (By similarity). (genecards.org)
  • Adrenergic receptors on cardiac fibroblasts were manipulated to examine the role of arrestin in the spatiotemporal regulation of extracellular signal-regulated kinase (ERK)1/2 MAPK signaling. (ahajournals.org)
  • A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. (asm.org)
  • Mel 1a melatonin receptor expression is regulated by protein kinase C and an additional pathway addressed by the protein kinase C inhibitor Ro 31-8220 in ovine pars tuberalis cells. (angelfire.com)
  • ISOP-induced 6-keto-PGF 1α synthesis was attenuated by C 2 -ceramide, an inhibitor of phospholipase D (PLD) by propranolol, a beta -AR antagonist that also inhibits phosphatidate phosphohydrolase and by the diacylglycerol lipase inhibitor 1,6-bis-(cyclohexyloximinocarbonylamino)-hexane (RHC 80267). (aspetjournals.org)
  • This stabilization was blocked by SB203580, an inhibitor of p38, and by two different dominant negative forms of MAPK-activated protein kinase 2 (MAPKAPK-2), a kinase lying downstream of p38. (asm.org)
  • In contrast to ATP, the number of cyclic AMP receptors is much more limited (PKA, PKG, PDE, CAP, CNG, EPAC/GEF), so a correspondingly selective inhibitor based on a cyclic nucleotide, such as Rp-cAMPS and its analogues would be much more focused on PKA, and thus have a clear advantage here. (biolog.de)
  • The mitogen-activated protein-kinase inhibitor PD098059 was used as a pharmacological tool to study the involvement of extracellular signal-regulated kinases in the induction of the acrosome reaction in human spermatozoa. (sun.ac.za)
  • Many G protein-coupled receptors (GPCRs) activate MAP kinases by stimulating tyrosine kinase signaling cascades. (uniprot.org)
  • In some systems, GPCRs stimulate tyrosine phosphorylation by inducing the "transactivation" of a receptor tyrosine kinase (RTK). (uniprot.org)
  • Pubmed ID: 12379128 G protein-coupled receptor kinases are well characterized for their ability to phosphorylate and desensitize G protein-coupled receptors (GPCRs). (jove.com)
  • G protein-coupled receptors (GPCRs) respond to diversified extracellular stimuli to modulate cellular function. (ahajournals.org)
  • Beta Adrenergic Receptor Kinase Activation Pathway. (wikidoc.org)
  • One such β-arrestin-mediated pathway uses the β 1 -adrenergic receptor (β 1 AR) to transactivate the EGFR. (pnas.org)
  • This receptor/effector pathway has been used in many studies to characterize the acute and chronic actions of opioids. (jneurosci.org)
  • Blumenau C, Berger E, Fauteck JD, Madeja M, Wittkowski W, Speckmann EJ and Musshoff U. Expression and functional characterization of the mt1 melatonin receptor from rat brain in Xenopus oocytes: evidence for coupling to the phosphoinositol pathway. (angelfire.com)
  • Unlike most receptors, Ptc activity turns off the downstream signaling pathway in the absence of ligand, and binding of Hh relieves that repression. (biologists.org)
  • Kinetics of the responses suggested that the responses to formoside and ectyoplasides A and B were receptor-mediated and capable of using the G αs signaling pathway in this system. (biologists.org)
  • It is unlikely that the pertussis toxin-sensitive pathway is activated by other, as yet unidentified FGF receptors since PDGF (platelet-derived growth factor)-stimulated MM14 cells expressing a chimeric receptor containing the FGF receptor-1 intracellular domain and the PDGF receptor extracellular domain were sensitive to pertussis toxin. (asm.org)
  • The mitogen-activated protein kinase (MAP kinase) pathway participates in a number of reactions of the cell when responding to various external stimuli. (sun.ac.za)
  • The beta(2)-adrenergic receptor mediates extracellular signal-regulated kinase activation via assembly of a multi-receptor complex with the epidermal growth factor receptor. (uniprot.org)
  • Abstract -β-Adrenergic modulation of the L-type Ca 2+ current ( I CaL ) was characterized for different developmental stages in murine embryonic stem cell-derived cardiomyocytes using the whole-cell patch-clamp technique at 37°C. Cardiomyocytes first appeared in embryonic stem cell-derived embryoid bodies grown for 7 days (7d). (ahajournals.org)
  • Activation of Gq coupled-receptor signaling leads to prolonged ERK1/2 MAPK phosphorylation, nuclear accumulation, and cellular proliferation. (ahajournals.org)
  • The chimeric transcript was stabilized by a constitutively active form of MAPK kinase 6, an activator of p38. (asm.org)
  • Several proinflammatory treatments which induce Cox-2 gene expression also stimulate the mitogen-activated protein kinase (MAPK) p38. (asm.org)
  • This kinase is activated by phosphorylation at threonine and tyrosine residues, catalyzed by the dual-specificity kinase MAPK kinase 6 (MKK6) ( 11 , 23 , 42 ). (asm.org)
  • Some protein kinases operate in more than one mitogen-activated protein-kinase (MAPK) cascade. (sun.ac.za)
  • The role of p38 mitogen-activated protein kinase (MAPK) in ischaemic preconditioning remains controversial. (sun.ac.za)
  • p38 Mitogen-activated protein kinase (p38 MAPK) is activated by short episodes of ischaemia-reperfusion as well as by sustained ischemia followed by reperfusion. (sun.ac.za)
  • 4 In order to examine the implications of these interactions to signaling, we used GTPγS binding and mitogen‐activated protein kinase (MAPK) phosphorylation assays and examined the effect of receptor activation on signaling. (deepdyve.com)
  • Addition of pertussis toxin also blocked FGF-2-mediated activation of mitogen-activated protein kinases (MAPKs). (asm.org)
  • In the rhodopsin system, which regulates rod cell function in the retina , rhodopsin kinase will phosphorylate serine and threonine residues on the rhodopsin receptor. (wikidoc.org)
  • beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi. (duke.edu)
  • Synaptic scaffolding molecule binds to and regulates vasoactive intestinal polypeptide type-1 receptor in epithelial cells. (springer.com)
  • Membrane-tethered AKT kinase regulates basal synaptic transmission and early phase LTP expression by modulation of post-synaptic AMPA receptor level. (semanticscholar.org)
  • Protein kinase A-mediated phosphorylation of the beta 2-adrenergic receptor regulates its coupling to Gs and Gi. (wikipedia.org)
  • Protein kinase Calpha negatively regulates systolic and diastolic function in pathological hypertrophy. (cdc.gov)
  • Cloning of the cDNA for the human beta 1-adrenergic receptor. (duke.edu)
  • Phosphorylation and desensitization of the human beta 1-adrenergic receptor. (semanticscholar.org)
  • phosphoinositide-3-kinase interacting pr. (broadinstitute.org)
  • Background- Signaling from phosphoinositide 3-kinase γ (PI3Kγ) is crucial for leukocyte recruitment and inflammation but also contributes to cardiac maladaptive remodeling. (ahajournals.org)
  • An emerging suitable candidate for therapeutic intervention could be phosphoinositide 3-kinase γ (PI3Kγ), a lipid and protein kinase expressed in both cardiac and bone marrow (BM)-derived cells. (ahajournals.org)
  • Functional regions of beta ARK are described with respect to their location within the exon-intron organization of the gene. (wikidoc.org)
  • This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. (nih.gov)
  • Association study of common variants within the G protein-coupled receptor kinase 6 gene and schizophrenia susceptibility in Han Chinese. (nih.gov)
  • GRK3 (G Protein-Coupled Receptor Kinase 3) is a Protein Coding gene. (genecards.org)
  • cAMP stimulates transcription of the beta 2-adrenergic receptor gene in response to short-term agonist exposure. (duke.edu)
  • cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor. (duke.edu)
  • The bek gene encodes a member of the high-affinity fibroblast growth factor receptor family. (duke.edu)
  • Shi, J.H., Zheng, B., Chen, S., Ma, G.Y. and Wen, J.K. (2012) Retinoic Acid Receptor Alpha Mediates All-Trans Retinoic Acid-Induced Klf4 Gene Expression by Regulating Klf4 Promoter Activity in Vascular Smooth Muscle Cells. (scirp.org)
  • Penn, R.B. and Benovic, J.L. (1994) Structure of the Human Gene Encoding the Beta-Adrenergic Receptor Kinase. (scirp.org)
  • Catecholamines, cardiac beta-adrenergic receptors, and heart failure. (duke.edu)
  • Agonist-promoted desensitization of adenylate cyclase is intimately associated with phosphorylation of the beta-adrenergic receptor in mammalian, avian, and amphibian cells. (duke.edu)
  • Beta-agonist- and prostaglandin E1-induced translocation of the beta-adrenergic receptor kinase: evidence that the kinase may act on multiple adenylate cyclase-coupled receptors. (duke.edu)
  • Beta adrenergic receptor kinase (also referred to as βARK or BARK ) is a serine/threonine intracellular kinase . (wikidoc.org)
  • step 7) βARK, itself a serine/threonine kinase, will then phosphorylate serine and threonine residues on the β-adrenergic receptor itself. (wikidoc.org)
  • Phosphorylation of Beta-3 adrenergic receptor at serine 247 by ERK MAP kinase drives lipolysis in obese adipocytes. (harvard.edu)
  • To examine these phenomena, we characterized agonist activation of ERK1/2 in HEK293 cells by the endogenous β 2 AR and in HEK293 cells stably overexpressing either the wild-type β 2 AR or a substitution mutant β 2 AR (PKA − ) that lacks the cyclic AMP-dependent protein kinase (PKA) consensus phosphorylation sites (S261A, S262A and S345A, S346A). (aspetjournals.org)
  • The present study examines receptor activation, desensitization, recovery from desensitization, and trafficking in locus ceruleus (LC) neurons from rats and mice after chronic treatment with morphine or methadone. (jneurosci.org)
  • Activation of the Cyclin B/Cdc2 kinase complex triggers entry into mitosis in all eukaryotic cells. (duke.edu)
  • Characterization of the murine BEK fibroblast growth factor (FGF) receptor: activation by three members of the FGF family and requirement for heparin. (duke.edu)
  • Furthermore, we demonstrate these actions are mediated by the activation of a G protein-coupled receptor. (frontiersin.org)
  • [11] Many of its effects are through activation of the melatonin receptor , while others are due to its role as an antioxidant . (wikipedia.org)
  • Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth. (springer.com)
  • NMDA receptor activation mediates hydrogen peroxide-induced pathophysiology in rat hippocampal slices. (angelfire.com)
  • 1 This is followed by the phosphorylation of the Ca 2+ channel through the activation of cAMP-dependent protein kinase A (PKA), 2 3 leading to an increase in channel open probability and channel availability. (ahajournals.org)
  • Cooperation of taurine uptake and dopamine D1 receptor activation facilitates the induction of protein synthesis-dependent late LTP. (semanticscholar.org)
  • Viagra for your synapses: Enhancement of hippocampal long-term potentiation by activation of beta-adrenergic receptors. (semanticscholar.org)
  • Activation of beta adrenergic receptors in the isolated rabbit heart by catecholamines stimulates prostacyclin (PGI 2 ) synthesis, which is inhibited by adenosine 3′5′-cyclic monophosphate (cAMP). (aspetjournals.org)
  • The purpose of this study was to determine if activation of beta adrenergic receptors in cultured coronary endothelial cells (CEC) of rabbit heart with isoproterenol (ISOP) stimulates PGI 2 synthesis and if cAMP inhibits the synthesis of this prostanoid and to investigate the underlying mechanism. (aspetjournals.org)
  • These data suggest that beta adrenergic receptors activation promotes PGI 2 synthesis in the CEC by selective activation of PLD and that cAMP decreases PGI 2 synthesis by decreasing PLD activity. (aspetjournals.org)
  • PG synthesis elicited by adrenergic transmitter in the heart is mediated by activation of beta -AR ( Shaffer and Malik, 1982 ). (aspetjournals.org)
  • The differential substrate preferences and activation modes of the distinct PI 3-kinase classes have important consequences for their functions. (biologists.org)
  • BMP signaling is initiated by binding of ligand to, and activation of, BMP type I (BMPRI) and type II (BMPRII) receptors. (biologists.org)
  • Activation of PKA is actually initiated at the exterior surface of heart cells where neurotransmitters and hormones bind to beta-adrenergic receptors. (innovations-report.com)
  • Signaling mediates cAMP-dependent activation of protein kinase PKA. (genecards.org)
  • Mediates vasodilatation after activation of beta-adrenergic receptors by isoproterenol (PubMed:17916776). (genecards.org)
  • Both α 1 -adrenergic receptor (α 1 ARs) and βARs are expressed in cardiac tissue and are activated by catecholamines to modulate maladaptive cardiac remodeling, including cardiac fibroblast proliferation, by activation of distinct pathways. (ahajournals.org)
  • 6 In order to explore the physiological consequences of this interaction, we examined the effect of receptor activation on the extent of Src and STAT3 phosphorylation and neuritogenesis in Neuro‐2A cells. (deepdyve.com)
  • 7 We find that the simultaneous activation of μ opioid and CB1 cannabinoid receptors leads to a significant attenuation of the response seen upon activation of individual receptors, implicating a role for receptor-receptor interactions in modulating neuritogenesis. (deepdyve.com)
  • Inhibitors of protein kinase A and protein kinase C also block odorant-induced desensitization and phosphorylation. (pnas.org)
  • Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine. (expasy.org)
  • Whole-cell, voltage-clamp patch clamp electrophysiology experiments were performed in HEK 293 cells transiently co-expressing wild-type (WT) or mutant KCNQ1 (mutations conferring mimics of dephosphorylation and phosphorylation were introduced at phosphorylation sites identified by LCMS/MS) and KCNE1 (auxiliary subunit) during ISO treatment, treatment with CaMKII or protein kinase A (PKA) inhibitors, or during lentiviral δCaMKII overexpression. (purdue.edu)
  • Strikingly, casein kinase II (CK2) inhibitors normalize increased NMDAR currents of dorsal horn neurons in nerve-injured rats. (aspetjournals.org)
  • Inhibitors have been very useful for characterizing the functions of PI 3-kinases in mammalian cells. (biologists.org)
  • Disadvantages and Potential Pitfalls of Protein Kinase A Inhibitors Blocking the Catalytic Subunit of Protein Kinase A ( e.g. (biolog.de)
  • Although the selectivity of ATP-site inhibitors of PKA, such as H 89 or KT 5720, seems to be rather good with respect to protein kinases C and G, this does obviously not hold true for other protein kinases. (biolog.de)
  • Our findings demonstrate that Alp and Car are ligands that not only act as classical receptor antagonists, but can also stimulate signaling pathways in a G protein-independent, β-arrestin-dependent fashion. (pnas.org)
  • Hoffman BB (2001) Catecholamines, sympathetic drugs, and adrenergic receptor antagonists. (els.net)
  • They also suggest that the GRK/arrestin system, rather than serving as a primary mediator of acute desensitization, controls recovery from desensitization by regulating receptor reinsertion to the plasma membrane after chronic treatment with morphine. (jneurosci.org)
  • The BEK/FGFR-2 receptor is a membrane-spanning tyrosine kinase with the typical features of FGF receptors. (duke.edu)
  • Membrane receptors for neuromodulators (NM) are highly regulated in their distribution and efficacy - a phenomenon which influences the individual cell's response to central signals of NM release. (cogprints.org)
  • These receptors are defined by a common structural feature which is comprised of seven hydrophobic trans-membrane segments. (researchimpact.com)
  • Membrane-associated guanylate kinases regulate adhesion and plasticity at cell junctions. (springer.com)
  • Drosophila has a single Hh ligand, which binds to its receptor, the multiple membrane-spanning protein Patched (Ptc). (biologists.org)
  • Recent studies have provided significant insights into the roles of PI 3-kinases, their catalytic products and their downstream effectors in membrane trafficking. (biologists.org)
  • By contrast, class III PI 3-kinases mainly mediate receptor-independent trafficking events, which mostly are related to endocytic membrane traffic, phagosome maturation and autophagy. (biologists.org)
  • In this Commentary, we highlight the functions of PI 3-kinases in membrane trafficking. (biologists.org)
  • The σ receptor is a poorly understood membrane protein expressed throughout the human body. (bioportfolio.com)
  • Thus, we have examined the role of beta-arrestin2 in the betaAR-mediated ERK signaling pathways. (nih.gov)
  • Genetic studies of the signaling pathways that regulate development have led to the view that a few evolutionarily conserved signaling pathways - the bone morphogenetic protein (Bmp), Wnt, receptor tyrosine kinase, Notch and Hedgehog (Hh) pathways - are used repeatedly in different contexts to control many cell fate decisions in all animals. (biologists.org)
  • Adenylyl cyclases are important effectors of transmembrane signaling pathways and are regulated by the activity of G protein coupled receptor signaling. (genecards.org)
  • Molecular pharmacology and modeling of vasopressin receptors. (wikipedia.org)
  • This assembly is the most diverse among the cell surface receptors. (researchimpact.com)
  • Adrenergic receptors are cell‐surface receptors for two major catecholamine hormones and neurotransmitters that regulate key physiological responses, including cardiovascular and pulmonary functions. (els.net)
  • A ubiquitously expressed G-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of BETA-ADRENERGIC RECEPTORS and a variety of other G-PROTEIN-COUPLED RECEPTORS. (bioportfolio.com)
  • Moreover, multiple members of the GRK family are able to phosphorylate the beta(2)AR and induce beta-arrestin recruitment, with their relative contributions largely determined by their relative expression levels. (duke.edu)
  • PI 3-kinases phosphorylate PtdIns or PIs at the 3-position of the inositol ring ( Fig. 1 ). (biologists.org)
  • I KACh is a heterotetrameric G-protein coupled inward rectifying K + channel (GIRK) composed of (GIRK1) 2 /(GIRK4) 2 subunits, activated in response to the binding of the βγ-subunit of the heterotrimeric G-protein, G i2 , which is released after the binding of ACh to the M 2 muscarinic receptor ( 7 , 8 ). (diabetesjournals.org)
  • We found that Gβγ subunits are likely to be involved since the expression of the C terminus of β-adrenergic receptor kinase 1, a Gβγ subunit-sequestering agent, promotes differentiation in the presence of FGF-2, and expression of the free Gβγ dimer can replace FGF-2, rescuing cells from pertussis toxin-induced differentiation. (asm.org)
  • To determine whether β-adrenergic ligands that do not activate G protein signaling (i.e., β-blockers) can stabilize the β 1 AR in a signaling conformation, we screened 20 β-blockers for their ability to stimulate β-arrestin-mediated EGFR transactivation. (pnas.org)
  • Recent evidence suggests that binding of different ligands promotes distinct receptor conformations leading to specific signaling events ( 9 - 12 ). (pnas.org)
  • We screened β-adrenergic ligands to determine if any could lead to β 1 AR-mediated EGFR transactivation. (pnas.org)
  • Ligands, such as prostaglandin E 2 (PGE 2 ), that activate G α s -coupled receptors generate cAMP in the cytosol and should lead to the exact same set of cellular responses as epinephrine, but they do not. (aspetjournals.org)
  • Ligands targeting the σ receptor are in clinical trials for treatment of Alzheimer's disease, ischemic str. (bioportfolio.com)
  • although some genes encoding putative receptors are known ( Buck and Axel, 1991 ), their specific ligands remain largely unidentified. (biologists.org)
  • 1989) Molecular characterization of the human beta 3‐adrenergic receptor. (els.net)
  • These findings, together with the demonstration that agents that reduce cAMP levels increase ISOP-induced PGI 2 synthesis, suggest that cAMP acts as an inhibitory modulator of beta -AR-stimulated PGI 2 synthesis in the heart ( Williams and Malik, 1989 ). (aspetjournals.org)
  • Role of phosphorylation in agonist-promoted beta 2-adrenergic receptor sequestration. (wikipedia.org)
  • Further studies revealed that recruitment of arrestin3 to the β 2 -adrenergic receptor orchestrates the sequestration of Gq-coupled receptor-induced ERK to the cytosol through direct binding of ERK to arrestin. (ahajournals.org)
  • When a phosphorylated peptide was fused to the C-terminal region of the mutant receptor, mimicking GRK-mediated phosphorylation, β-arrestin protein recruitment and biased signaling were recovered. (sciencemag.org)
  • BACKGROUND: Impaired myocardial beta-adrenergic receptor (betaAR) signaling, including desensitization and functional uncoupling, is a characteristic of congestive heart failure. (duke.edu)
  • Long-term beta-blocker treatment, including the use of carvedilol, improves myocardial betaAR signaling and reduces betaARK1 levels in a specific and dose-dependent manner. (duke.edu)
  • demonstrate for the first time exosomal enrichment of G-protein-coupled receptor kinase (GRK) 5 and GRK6, both of which regulate Src and IGF-IR signaling and have been implicated in cancer. (nih.gov)
  • Recent evidence suggests that binding of agonist to its cognate receptor initiates not only classical G protein-mediated signaling, but also β-arrestin-dependent signaling. (pnas.org)
  • Beta-adrenergic receptors (βARs) are members of the seven transmembrane receptor (7TMR) family that become activated upon catecholamine binding to stimulate G protein-dependent signaling. (pnas.org)
  • There was no effect of PMU on β 2 AR-cAMP signaling in RII_Protein Kinase A domains. (frontiersin.org)
  • Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. (abcam.com)
  • 5 Despite recent advances in the understanding of the β-adrenergic modulation of the Ca 2+ channel during embryonic 6 and postnatal development, 7 the establishment of this important signaling cascade during cardiomyocyte development is still unresolved. (ahajournals.org)
  • The aim of the present study was to investigate the establishment of the β-adrenergic signaling cascade for early cardiomyocyte development. (ahajournals.org)
  • ERK and mTOR signaling couple beta-adrenergic receptors to translation initiation machinery to gate induction of protein synthesis-dependent long-term potentiation. (semanticscholar.org)
  • In addition to that, post-receptor components of β-AR signaling seem to have a role in AD pathogenesis. (iospress.com)
  • Furthermore, we show BMP-dependent physical interaction of VE-cadherin with the BMP receptor ALK2 (BMPRI) and BMPRII, resulting in stabilization of the BMP receptor complex and, thereby, the support of BMP6-Smad signaling. (biologists.org)
  • Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. (semanticscholar.org)
  • β-adrenergic receptor-mediated cardiac contractility is inhibited via vasopressin type 1A-receptor-dependent signaling. (semanticscholar.org)
  • PKA actually activates other kinases, which in effect amplify the effect of PKA through a signaling cascade. (innovations-report.com)
  • Catalyzes the formation of the signaling molecule cAMP downstream of G protein-coupled receptors (PubMed:17916776, PubMed:17110384). (genecards.org)
  • Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells (PubMed:17916776). (genecards.org)
  • Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption. (genecards.org)
  • Interestingly, coactivation of these receptors with the β-adrenergic receptors induced transient ERK signaling localized within the cytosol, which attenuated cell proliferation. (ahajournals.org)
  • Additionally, high-affinity binding and subsequent signaling events require that FGFs bind to both the tyrosine kinase and a heparan sulfate proteoglycan ( 49 , 53 , 54 ). (asm.org)
  • The structure of βARK1 consists of a protein of 689 amino acids (79.7 kilodaltons) with a protein kinase catalytic domain that bears greatest sequence similarity to protein kinase C and the cyclic adenosine monophosphate (cyclic AMP)-dependent protein kinase. (wikidoc.org)
  • Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the protein kinase catalytic domain having 95% similarity. (genecards.org)
  • nuclear receptor subfamily 2, group E, m. (broadinstitute.org)
  • Tyrosine protein kinases belonging to the Btk/Itk/Tec subfamily. (ebi.ac.uk)
  • A contributing mechanism for this impairment may involve enhanced myocardial beta-adrenergic receptor kinase (betaARK1) activity because levels of this betaAR-desensitizing G protein-coupled receptor kinase (GRK) are increased in heart failure. (duke.edu)
  • The protein kinase C (PKC) family is implicated in cardiac hypertrophy, contractile failure, and beta-adrenergic receptor (betaAR) dysfunction. (cdc.gov)
  • Coincident with EGFR transactivation, isoproterenol exposure induces the formation of a multireceptor complex containing both the beta(2)AR and the "transactivated" EGFR. (uniprot.org)
  • Additionally, a mutant of the receptor, which lacks the sites normally phosphorylated by PKA, can activate adenylyl cyclase, the enzyme that generates cAMP, but not MAP kinase. (nih.gov)
  • First, a localized signal is generated by a G protein-coupled receptor paired to one or more of the nine different transmembrane adenylyl cyclase isoforms that generate the cAMP signal in the cytosol. (aspetjournals.org)
  • Thus, the pharmacological reality is that at least 20-30 of these receptors couple G α s , stimulate adenylyl cyclase (AC) activity, and promote cAMP production. (aspetjournals.org)
  • On the basis of this evidence, it is suggested that an increase in oxidative stress during both the ischemic and reperfusion phases may play an important role in the alteration of β-adrenergic receptors, the adenylyl cyclase and G s -protein system, and the attenuation of the inotropic responses of the ischemic-reperfused hearts to catecholamines. (springer.com)
  • AGC Ser/Thr protein kinase family. (abcam.com)
  • In particular, the G protein coupled receptor kinase 2, responsible for β-AR desensitization and downregulation, mediates amyloid-induced β-AR dysfunction in neurons, and its levels in circulating lymphocytes of AD patients are increased and inversely correlated with patient's cognitive status. (iospress.com)
  • By using mutants of the β 1 AR lacking G protein-coupled receptor kinase phosphorylation sites and siRNA directed against β-arrestin, we show that Alp- and Car-stimulated EGFR transactivation requires β 1 AR phosphorylation at consensus G protein-coupled receptor kinase sites and β-arrestin recruitment to the ligand-occupied receptor. (pnas.org)
  • 1987) Ligand binding to the beta‐adrenergic receptor involves its rhodopsin‐like core. (els.net)
  • Structural basis for σ receptor ligand recognition. (bioportfolio.com)
  • Ligand-directed serotonin 5-HT receptor desensitization, β-arrestin recruitment, and sensitization. (bioportfolio.com)
  • Increased N -methyl- d -aspartate receptor (NMDAR) activity and phosphorylation in the spinal cord are critically involved in the synaptic plasticity and central sensitization associated with neuropathic pain. (aspetjournals.org)
  • S-SCAM/MAGI-2 is an essential synaptic scaffolding molecule for the GluA2-containing maintenance pool of AMPA receptors. (springer.com)
  • To define the cell types involved in this protection, bone marrow chimeras, lacking kinase activity in the immune system or the heart, were studied after transverse aortic constriction. (ahajournals.org)
  • Here we use the beta(2)-adrenergic receptor (beta(2)AR), the archetypal nonvisual heptahelical receptor, as a model to test functional GRK specificity. (duke.edu)
  • Surprisingly, the GRK specificity for beta-arrestin recruitment does not correlate with that for bulk receptor phosphorylation, indicating that beta-arrestin recruitment is specific for a subset of receptor phosphorylations on specific sites. (duke.edu)
  • Evidence for G protein-coupled receptor kinase specificity. (semanticscholar.org)
  • In enzymology, a beta-adrenergic-receptor kinase (EC is an enzyme that catalyzes the chemical reaction: ATP + [beta-adrenergic receptor] ⇌ {\displaystyle \rightleftharpoons } ADP + phospho-[beta-adrenergic receptor] Thus, the two substrates of this enzyme are ATP and beta-adrenergic receptor, whereas its two products are ADP and phospho-beta-adrenergic receptor. (wikipedia.org)
  • The systematic name of this enzyme class is ATP:[beta-adrenergic receptor] phosphotransferase. (wikipedia.org)
  • A beta-adrenergic receptor kinase-like enzyme is involved in olfactory signal termination. (pnas.org)
  • subicular neurons via presynaptic D1-like dopamine receptors. (cogprints.org)
  • Phosphorylation and desensitization of human endothelin A and B receptors. (semanticscholar.org)
  • Effect of different G protein-coupled receptor kinases on phosphorylation and desensitization of the alpha1B-adrenergic receptor. (semanticscholar.org)
  • Furthermore, defibrotide prevents the decline of beta-adrenergic receptor function, a phenomenon related to excessive circulating catecholamines that occurs during the myocardial infarct. (biomedsearch.com)
  • If one bathes cells in a catecholamine, such as epinephrine, β -adrenergic receptors are activated and a cAMP signal is generated in the cytosol. (aspetjournals.org)
  • Gannon, A.M., Turner, E.C., Reid, H.M. and Kinsella, B.T. (2009) Regulated Expression of the Alpha Isoform of the Human Thromboxane A2 Receptor during Megakaryocyte Differentiation: A Coordinated Role for WT1, Egr1, and Sp1. (scirp.org)
  • Ser/Thr protein kinases such as the Akt/Rac family, the beta-adrenergic receptor kinases, the mu isoform of PKC and the trypanosomal NrkA family. (ebi.ac.uk)
  • The sympathetic nervous system increases norepinephrine release to stimulate β-adrenergic receptors (βARs) located on heart cell (cardiomyocyte) membranes to increase the heart's rate and force of contraction. (wikipedia.org)
  • Properties of the beta 1- and beta 2-adrenergic receptor subtypes revealed by molecular cloning. (wikipedia.org)