Dihydroalprenolol: 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.Receptors, Adrenergic, beta: 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.Receptors, Adrenergic: 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.Propranolol: 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.Isoproterenol: 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.Butoxamine: A beta-2 selective adrenergic antagonist. It is used primarily in animal and tissue experiments to characterize BETA-2 ANDRENERGIC RECEPTORS.Adrenergic beta-Antagonists: 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.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.beta-Adrenergic Receptor Kinases: G-protein-coupled receptor kinases that mediate agonist-dependent PHOSPHORYLATION and desensitization of BETA-ADRENERGIC RECEPTORS.Receptors, Adrenergic, beta-2: 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.G-Protein-Coupled Receptor Kinase 2: 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.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.Cyclic AMP: 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.Metoprolol: A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.G-Protein-Coupled Receptor Kinase 5: 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.Norepinephrine: 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.Epinephrine: 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.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.G-Protein-Coupled Receptor Kinase 3: 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.Receptors, Adrenergic, beta-1: 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.Cyclic AMP-Dependent Protein Kinases: 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.Receptors, Adrenergic, alpha-2: 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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Receptors, Adrenergic, alpha: 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.Receptors, Adrenergic, alpha-1: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Dogs: 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)Phosphatidylinositol 3-Kinases: 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.Receptors, Adrenergic, beta-3: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.G-Protein-Coupled Receptor Kinase 1: 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.MAP Kinase Signaling System: 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.Adrenergic beta-2 Receptor Agonists: Compounds bind to and activate ADRENERGIC BETA-2 RECEPTORS.G-Protein-Coupled Receptor Kinase 4: 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.Arrestins: Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors.Adrenergic beta-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.Signal Transduction: 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.Adrenergic alpha-Agonists: Drugs that selectively bind to and activate alpha adrenergic receptors.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.Calcium-Calmodulin-Dependent 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)src-Family Kinases: 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.Molecular Sequence Data: 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-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Adrenergic alpha-Antagonists: 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.Protein Kinase C: 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.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Adrenergic alpha-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION.Propanolamines: AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.Kinetics: The rate dynamics in chemical or physical systems.Transfection: 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.Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors.Amino Acid Sequence: 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.Adrenergic Antagonists: Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.GTP-Binding Proteins: 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.-.Adrenergic beta-3 Receptor Agonists: Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.Mitogen-Activated Protein Kinase 1: 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.p38 Mitogen-Activated Protein Kinases: 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.Enzyme Activation: 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, Cultured: 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.Receptor, Insulin: 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.Mitogen-Activated Protein Kinase 3: 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.Interleukin-1beta: 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.Adrenergic alpha-1 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-1 RECEPTORS.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Adrenergic beta-1 Receptor Agonists: Compounds that bind to and activate ADRENERGIC BETA-1 RECEPTORS.Iodocyanopindolol: A highly selective and specific beta antagonist that is used to characterize beta-adrenoceptors.Mutation: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.RNA, Messenger: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Mitogen-Activated Protein Kinase Kinases: 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.Protein Binding: 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.Adrenergic alpha-2 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.JNK Mitogen-Activated Protein Kinases: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Pindolol: 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)Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Adrenergic beta-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-1 RECEPTORS.Clonidine: An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.Blotting, Western: 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.p21-Activated Kinases: 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 Fusion Proteins: 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.Mitogen-Activated Protein Kinases: 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).Adrenergic alpha-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.Extracellular Signal-Regulated MAP Kinases: 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.CHO Cells: 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.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.MAP Kinase Kinase Kinases: 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).Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Idazoxan: A benzodioxane-linked imidazole that has alpha-2 adrenoceptor antagonist activity.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Dioxanes: 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)Rats, Sprague-Dawley: 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.beta 2-Microglobulin: 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.Creatine Kinase: 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.Protein Structure, Tertiary: 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.Glycogen Synthase Kinase 3: 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.PhosphoproteinsCDC2 Protein Kinase: 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.Cyclin-Dependent Kinases: 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.Myocardium: 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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Casein Kinase II: 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.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Ribosomal Protein S6 Kinases: 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.Down-Regulation: 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.eIF-2 Kinase: 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.Casein Kinases: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cloning, Molecular: 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.Gene Expression Regulation: 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.Phenylephrine: An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Pyruvate Kinase: 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 2.7.1.40.Calcium: 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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Receptor, Epidermal Growth Factor: 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.Proto-Oncogene Proteins: 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.Cattle: 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.Insulin: 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).Binding, Competitive: 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.Ligands: 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)Adrenergic beta-3 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-3 RECEPTORS.MAP Kinase Kinase 1: An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Mice, Knockout: 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.Immunoblotting: 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.Serine: 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.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Proto-Oncogene Proteins c-akt: 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.Thymidine Kinase: 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 2.7.1.21.Transforming Growth Factor beta: 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.Brassinosteroids: Plant steroids ubiquitously distributed throughout the plant kingdom. They play essential roles in modulating growth and differentiation of cells at nanomolar to micromolar concentrations.MAP Kinase Kinase 4: 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.Precipitin Tests: 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.Tumor Cells, Cultured: 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.Integrin beta3: 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.Clenbuterol: A substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma.Models, Biological: 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.COS Cells: 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).)Mice, Inbred C57BLArrestin: 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.DioxolesTetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Cell Line, Tumor: A cell line derived from cultured tumor cells.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.Pertussis Toxin: 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.Receptors, Cell Surface: 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, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.1-Phosphatidylinositol 4-Kinase: 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.Protein Transport: 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.Arabidopsis Proteins: 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.GTP-Binding Protein alpha Subunits, Gi-Go: 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.Steroids, Heterocyclic: Steroidal compounds in which one or more carbon atoms in the steroid ring system have been substituted with non-carbon atoms.I-kappa B Kinase: 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.GTP-Binding Protein alpha Subunits, Gs: A family of heterotrimeric GTP-binding protein alpha subunits that activate ADENYLYL CYCLASES.DNA Primers: 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.Phosphotyrosine: 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.Imidazoles: 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).CDC2-CDC28 Kinases: 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.Membrane Proteins: 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.Apoptosis: 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.rho-Associated Kinases: 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.Rhodopsin: 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.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Aurora Kinases: 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.Protein Kinase C-alpha: 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.Protein Kinase C-delta: 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.Structure-Activity Relationship: 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.Protein Conformation: 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).Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Alprenolol: One of the ADRENERGIC BETA-ANTAGONISTS used as an antihypertensive, anti-anginal, and anti-arrhythmic agent.Arabidopsis: 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.Adrenergic Agents: 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.Virulence Factors, Bordetella: 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.Indoles: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Intracellular Signaling Peptides and Proteins: 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.Heterotrimeric GTP-Binding Proteins: 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.3T3 Cells: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Reverse Transcriptase Polymerase Chain Reaction: 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, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Macromolecular Substances: 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.AMP-Activated Protein Kinases: 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.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Threonine: 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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Carbazoles: Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.Diacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.Protein Kinase C beta: 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.Ethanolamines: AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.DNA, Complementary: 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.Focal Adhesion Kinase 1: 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.

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 ...
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 ...
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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 ...
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 mechanisms of desensitization and resensitization of the dopamine D1 receptor are not well understood. Although the high homology of the D1 receptor with the β2-adrenergic receptor might indicate that similar mechanisms regulate the responsiveness of the receptors, even subtypes of β-adrenergic receptors differ substantially in this respect (Shiina et al., 2000). For β-adrenergic receptors, a distinction has been made between desensitization that is homologous (resulting from stimulation of the same receptor) or heterologous (resulting from stimulation of a different receptor subtype, or nonreceptor-mediated activation of a second messenger) (Harden, 1983). A mechanism for heterologous desensitization is phosphorylation of the receptor by PKA (Clark et al., 1989; Hausdorff et al., 1989), whereas homologous desensitization of the β2-adrenergic receptor involves phosphorylation of the agonist-occupied receptor by both GRK (Benovic et al., 1986) and PKA (Post et al., 1996; Moffett et al., ...
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 ...
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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
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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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.
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 ...
TY - JOUR. T1 - Paeoniflorin inhibits proliferation of fibroblast-like synoviocytes through suppressing G-protein-coupled receptor kinase 2. AU - Chen, Jing Yu. AU - Wu, Hua Xun. AU - Chen, Yin. AU - Zhang, Ling Ling. AU - Wang, Qingtong. AU - Sun, Wu Yi. AU - Wei, Wei. PY - 2012/3/13. Y1 - 2012/3/13. N2 - Paeoniflorin (Pae) is a monoterpene glucoside and the main component of the total glucosides of paeony (TGP) extracted from the roots of Paeonia lactiflora. Its anti-inflammatory effect is associated with regulating G-protein-coupled receptors (GPCRs) signaling. The aim of this study was to explore the expression change of G-protein-coupled receptor kinase 2 (GRK2) in fibroblast-like synoviocytes (FLS) and the effect of Pae. Pae was obtained and purified from the roots of Paeonia lactiflora. We investigated the expression of GRK2 in synovium during the inflammatory process and assessed the effects of a specific GRK2 inhibitor and Pae on proliferation, cAMP level, and protein kinase A (PKA) ...
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 ...
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 ...
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.
This Histri was built automatically but not manually verified. As a consequence, the Histri can be incomplete or can contain errors ...
This gene encodes a member of the GIT protein family, which interact with G protein-coupled receptor kinases and possess ADP-ribosylation factor (ARF) GTPase-activating protein (GAP) activity. GIT proteins traffic between cytoplasmic complexes, focal adhesions, and the cell periphery, and interact with Pak interacting exchange factor beta (PIX) to form large oligomeric complexes that transiently recruit other proteins. GIT proteins regulate cytoskeletal dynamics and participate in receptor internalization and membrane trafficking. This gene has been shown to repress lamellipodial extension and focal adhesion turnover, and is thought to regulate cell motility. This gene undergoes extensive alternative splicing to generate multiple isoforms, but the full-length nature of some of these variants has not been determined. The various isoforms have functional differences, with respect to ARF GAP activity and to G protein-coupled receptor kinase 2 binding. [provided by RefSeq, Sep 2008 ...
The major finding of this study is that GIT1 is an important regulator of vascular remodeling. Specifically, we found that GIT1 depletion inhibited intima formation after carotid ligation by 50%. In vivo and in vitro analysis showed a key role for GIT1 in VSMC proliferation, migration, and apoptosis during vascular remodeling (Figure III in the online-only Data Supplement). Furthermore, GIT1 is required for VSMC proliferation through PLCγ and ERK1/2 by regulating the expression of cell cycle-related proteins, such as cyclin D1. GIT1 is also essential for cell survival by regulating VSMC apoptosis through PLCγ and cell migration through PLCγ and ERK1/2.. VSMC proliferation and migration are key components in vascular remodeling.1,2 The present study shows that GIT1 expression is highly regulated by AngII and PDGF in vitro, and during vascular remodeling in vivo. The role of GIT1 in mediating VSMC proliferation was demonstrated by several assays, including in vitro cell count, [3H]-thymidine ...
Increasing evidence suggests to vascular damage as an early contributor to the development of two leading causes of age-associated dementia, namely Alzheimer disease (AD) and AD-like pathology such as stroke. This review focuses on the role of G protein-coupled receptor kinases, particularly GRK2 as they relate to dementia and how the vascular abnormalities is involved in cerebrovascular pathogenesis. Any possible involvement of GRKs in AD pathogenesis is an interesting notion, whose exploration may help bridge the gap in our understanding of the heart-brain connection in relation to neurovisceral damage and vascular complications in AD. The a priori basis for this inquiry stems from the fact that kinases of this family regulate numerous receptor functions in the brain, the myocardium and elsewhere. The aim of this review is to discuss the finding of GRK2 overexpression in the context of the early AD pathogenesis, since increased levels of GRK2 immunoreactivity were found in vulnerable neurons from AD
GIT2 - GIT2 (Myc-DDK-tagged)-Human G protein-coupled receptor kinase interacting ArfGAP 2 (GIT2), transcript variant 6 available for purchase from OriGene - Your Gene Company.
Sucrose as a product of photosynthesis is the major carbohydrate translocated from photosynthetic leaves to growing nonphotosynthetic organs such as roots and seeds. These growing tissues, besides carbohydrate supply, require uptake of water through aquaporins to enhance cell expansion during growth. Previous work revealed Sucrose Induced Receptor Kinase, SIRK1, to control aquaporin activity via phosphorylation in response to external sucrose stimulation. Here, we present the regulatory role of AT3G02880 (QSK1), a receptor kinase with a short external domain, in modulation of SIRK1 activity. Our results suggest that SIRK1 autophosphorylates at Ser-744 after sucrose treatment. Autophosphorylated SIRK1 then interacts with and transphosphorylates QSK1 and QSK2. Upon interaction with QSK1, SIRK1 phosphorylates aquaporins at their regulatory C-terminal phosphorylation sites. Consequently, in root protoplast swelling assays, the qsk1qsk2 mutant showed reduced water influx rates under iso-osmotic ...
Chen Xuewei,Shang Junjun,Chen Dexi,et al. a b-lectin receptor kinase gene conferring rice blast resistance[J]. Plant Journal,2006-01-01,46(5):794-804 ...
Compare G Protein-coupled Receptor 113 ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, reviews, and more.
Purchase G Protein-Coupled Receptors: Emerging Paradigms in Activation, Signaling and Regulation Part A, Volume 338 - 1st Edition. Print Book. ISBN 9780128137727
Stimulation of Gi-coupled receptors leads to the activation of mitogen-activated protein kinases (MAP kinases). In several cell types, this appears to be dependent on the activation of p21ras (Ras). Which G-protein subunit(s ...
TY - JOUR. T1 - Multiple kinases phosphorylate the pancreatic cholecystokinin receptor in an agonist-dependent manner. AU - Gates, L. K.. AU - Ulrich, C. D.. AU - Miller, L. J.. PY - 1993/1/1. Y1 - 1993/1/1. N2 - The cholecystokinin (CCK) receptor on the rat pancreatic acinar cell is a guanine nucleotide-binding protein (G protein)-coupled receptor, which was recently demonstrated to be phosphorylated in response to agonist stimulation (Klueppelberg et al., J. Biol. Chem. 266: 17744-17746, 1991). In this work, we establish that this receptor is phosphorylated in response to a variety of homologous and heterologous secretagogues and that these phosphorylation events represent action by more than one protein kinase. One subgroup of kinases includes one or more isotype of protein kinase C (PKC), and is capable of playing a role in homologous and heterologous desensitization. A second subgroup of kinases that acts on the CCK receptor was defined by its resistance to 10 μM staurosporine, which was ...
In the current study, the most important question was whether GRK2 negatively controlled the insulin-induced Akt/eNOS pathway in aortas from diabetic mice with hyperinsulinemia. An important vascular action of insulin is its vasodilator effect, which is associated with increased NO production by endothelial cells (4,5,22,23). The results shown in the present Fig. 1A and B are consistent with our previous report (14). In that previous report, we discussed why GRK2 was increased in the diabetic aorta and how it affected the dysfunction of the endothelium-dependent relaxation to insulin that is mediated via the Akt pathway. We drew the conclusion that PKC activation mediated GRK2 overactivation and that the upregulation of GRK2 led to inhibition of the insulin-induced stimulation of the Akt/eNOS pathway (14). In the current study, we were interested in the pathway downstream of GRK2. From the results, we can propose that GRK2 acts by competing for β-arrestin 2 upon insulin-induced Akt/eNOS ...
Looking for online definition of probable G protein-coupled receptor 21 in the Medical Dictionary? probable G protein-coupled receptor 21 explanation free. What is probable G protein-coupled receptor 21? Meaning of probable G protein-coupled receptor 21 medical term. What does probable G protein-coupled receptor 21 mean?
rat G protein-coupled receptor AGR9: a mammalian receptor, member of the G protein-coupled receptor family; expressed in cardiovascular, CNS & digestive systems; amino acid sequence given in first source
Schematic picture of tropomyosin receptor kinases (Trks) and the p75 neurotrophin receptors (p75NTR). (A) Structure of the two receptors: The intracellular (on
Robert J. Lefkowitz and Brian K. Kobilka take home this year’s Nobel Prize for Chemistry for revealing how membrane receptors sense and respond to chemical signals.
The protein encoded by this gene is a member of the G protein-coupled receptor family; however, the specific function of this gene has not yet been determined.
The worlds first wiki where authorship really matters. Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts.
The worlds first wiki where authorship really matters. Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts.
Alpha-1-adrenergic receptors (alpha-1-ARs) are members of the G protein-coupled receptor superfamily. They activate mitogenic responses and regulate growth and proliferat
G protein-coupled receptors (GPCRs) comprise the largest family of cell surface signaling receptors in the mammalian genome, mediate cellular responses to diver...
Novel findings reveal that G protein-coupled receptors, which have previously assumed to be statically configured as monomers or dimers, can switch...
This support page will give you more information on the level of support offered for Ark - Multi Style, Animated & Retina Ready Tables that you can purchase from CodeCanyon.
387554453 - EP 1118621 A4 2003-06-25 - NOVEL G PROTEIN-COUPLED RECEPTOR PROTEIN AND DNA THEREOF - [origin: WO0020456A1] A human-origin G protein-coupled receptor protein or its peptide fragment or its salt, a nucleic acid encoding this receptor protein and its derivative, etc. The human hippocampus-origin G protein-coupled receptor protein or the nucleic acid encoding the same and its derivative are usable in determining a ligand (an agonist) to the G protein-coupled receptor protein, as preventives and/or remedies for diseases in association with dysfunction of the G protein-coupled receptor protein, as gene diagnostics, in a method for screening a compound capable of varying the expression dose of the G protein-coupled receptor protein or its peptide fragment, etc.[origin: WO0020456A1] A human-origin G protein-coupled receptor protein or its peptide fragment or its salt, a nucleic acid encoding this receptor protein and its derivative, etc. The human hippocampus-origin G protein-coupled receptor
John Tesmer, a research associate professor at the Life Sciences Institute and the department of pharmacology at the University of Michigan Medical School, has been named the winner of the 2010 American Society for Biochemistry and Molecular Biology Young Investigator Award (formerly known as the ASBMB/Schering-Plough Research Institute Award), which honors outstanding research contributions to biochemistry and molecular biology by individuals who have no more than 15 years of postdoctoral experience.. Tesmer will present an award lecture titled "Structural Analysis of Heterotrimeric G Proteins and G Protein-Coupled Receptor Kinases" at 8:30 a.m. Monday, April 26, at the 2010 annual meeting in Anaheim, Calif.. G protein-coupled receptor signaling pathways are responsible for a wide range of intracellular events and are an intense area of biological and pharmaceutical study. Researchers studying GPCR owe a lot to Tesmer and his group, who provided insight into GPCR signaling through their ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the GIT protein family, which interact with G protein-coupled receptor kinases and possess ADP-ribosylation factor (ARF) GTPase-activating protein (GAP) activity. GIT proteins traffic between cytoplasmic complexes, focal adhesions, and the cell periphery, and interact with Pak interacting exchange factor beta (PIX) to form large oligomeric complexes that transiently recruit other proteins. GIT proteins regulate cytoskeletal dynamics and participate in receptor internalization and membrane trafficking. This gene has been shown to repress lamellipodial extension and focal adhesion turnover, and is thought to regulate cell motility. This gene undergoes extensive alternative splicing to generate multiple isoforms, but the full-length nature of some of these variants has not been determined. The various isoforms have functional differences, with respect to ARF GAP activity ...
The large‐scale production of recombinant G protein-coupled receptors (GPCRs) is one of the major bottlenecks that hamper functional and structural studies of this important class of integral membrane proteins
Activation of G protein-coupled receptors is involved in regulating many cellular responses, but less is known regarding the role of these receptors in the differentiation and maintenance of skeletal muscle. New findings implicate the inhibitor subunit Gαi2 as a vital mediator of myofiber maturation and growth, operating through multiple signaling pathways to selectively stimulate protein synthesis or inhibit cytokine-dependent protein turnover.. ...
Erratum to "Conformation of a double-membrane-spanning fragment of a G protein-coupled receptor: Effects of hydrophobic environment and pH" [Biochim. Biophys. Acta 1768 (2007) 1199-1210] Academic Article ...
Figure 12. GPCR and heterotrimeric G-protein signalling.. The ligand bound to the GPCR is shown in red. Binding allows the exchange of GDP for GTP by the associated G protein, and dissociation of the protein into Gα and Gβγ subunits. These then have downstream effects on a range of proteins, thereby propagating the signal from the bound ligand. Yellow arrows indicate either activation (up arrow) or inhibition (down arrow) of the targets. Regulators of G-protein signalling (RGS) proteins aid the GTPase activity of the G protein to turn off the signal. Arrestin can bind the receptor following GPCR phosphorylation by G-protein receptor kinase (GRK), desensitizing the receptor to further signalling. Reproduced from Berridge, M.J. (2012) Cell Signalling Biology; doi:10.1042/csb0001002, with permission. ...
Wet-lab validated real-time PCR primer assays for your biological pathway of interest. Select your gene target of interest using an interactive pathway map, and select your plate.
Wet-lab validated real-time PCR primer assays for your biological pathway of interest. Select your gene target of interest using an interactive pathway map, and select your plate.
GPR120 is a member of the rhodopsin family of G protein-coupled receptors (GPRs). This gene encodes a G protein-coupled receptor (GPR) which belongs to the rhodopsin fami
G Protein‐Coupled Receptor Genetics: Research and Methods in the Post‐Genomic Era features practical techniques inspired by the fast moving GPCR field. From powerful bioinformatic tools tracing the e
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 1996.; On t.p., "[beta]" appears as the lower case Greek letter. Vita.; Includes bibliographical references (leaves 166-207 ...
Morning Guys, I need to address few important issues here. Firstly, please make sure you do a thorough research on the topic before writing on the page. Believe me writing on the page is the easiest part. But finding and digesting the info, particularly in this topic is a little tough. The reason I said that is because Tyrosin Receptor Kinases are not restricted only in Neural cells, also involved in normal cells. so perhaps youd need to read more on that…?!!! Secondly, in order to make the most out of this group project, I personally believe that we should divide the topic evenly between four members of the group. This way wed ensure that 1) everybody has had a fair go. 2) Prevents further confusion. 3) Prevents waste of time and overlapping info. Hopefully during our peer-review session we can then follow members works easily without any confusion. For Now, Im advising everyone that I will be doing the Introduction that will include evolutionary info on Trk as well as its ...
Morning Guys, I need to address few important issues here. Firstly, please make sure you do a thorough research on the topic before writing on the page. Believe me writing on the page is the easiest part. But finding and digesting the info, particularly in this topic is a little tough. The reason I said that is because Tyrosin Receptor Kinases are not restricted only in Neural cells, also involved in normal cells. so perhaps youd need to read more on that…?!!! Secondly, in order to make the most out of this group project, I personally believe that we should divide the topic evenly between four members of the group. This way wed ensure that 1) everybody has had a fair go. 2) Prevents further confusion. 3) Prevents waste of time and overlapping info. Hopefully during our peer-review session we can then follow members works easily without any confusion. For Now, Im advising everyone that I will be doing the Introduction that will include evolutionary info on Trk as well as its ...
Much is known about the how Gβγ subunits regulate effectors in response to G protein-coupled receptor stimulation. However, there is still a lot we dont know ...
cdna chromosome:GRCm38:13:19749682:19824257:-1 gene:ENSMUSG00000053101 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Gpr141 description:G protein-coupled receptor 141 [Source:MGI Symbol;Acc:MGI:2672983 ...
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.
TY - JOUR. T1 - Skin fibroblast beta-adrenergic receptor function in manie-depressive illness. AU - Berrettini, Wade H.. AU - Bardakjian, Josiane. AU - Cappellari, Charles B.. AU - Barnett, Arthur L.. AU - Albright, Allen. AU - Nurnberger, John I.. AU - Gershon, Elliot S.. PY - 1987/12. Y1 - 1987/12. N2 - Beta-adrenergic receptor function was assessed in cultured skin fibroblasts obtained from bipolar patients and normal volunteers by measurement of the cyclic adenosine monophosphate (cAMP) response to isoproterenol. No group differences were observed. To assess regulation of receptor desensitization, fibroblasts were incubated for 24 hr with isoproterenol, and then the cAMP response to isoproterenol was determined. Subsensitivity to rechallenge with isoproterenol did not distinguish bipolar patients from controls.. AB - Beta-adrenergic receptor function was assessed in cultured skin fibroblasts obtained from bipolar patients and normal volunteers by measurement of the cyclic adenosine ...
This Teaching Resource provides lecture notes and slides for a class covering G protein-coupled receptors (GPCRs) and is part of the course "Cell Signaling Systems: A Course for Graduate Students." The lecture begins with a discussion of the major classes of GPCRs and then proceeds to describe the mechanisms of receptor diversity, ligand interaction, desensitization, coupling, and mutations associated with human diseases.. ...
Ready-to-use Adenovirus expressing Human LGR5 (leucine rich repeat containing G protein-coupled receptor 5). Available with optional GFP reporter or cell-specific promoter.
[ Paint Colors For Ark ] - Wooden Chair Official Ark Survival Evolved Wiki,Greenhouse Wall Official Ark Survival Evolved Wiki,Wooden Window Official Ark Survival Evolved Wiki
Lift Off", Amerikalı hip hop sanatçıları Kanye West ve Jay-Znin Watch the Throne (2011) adını taşıyan ortak albümlerinde yer alan bir şarkıdır. Beyoncénin ikiliye eşlik ettiği şarkının yazarlığını Kanye West, Jay-Z, Jeff Bhasker, Mike Dean, Bruno Mars ve Seal Samuel; prodüktörlüğünü West, Bhasker, Dean, Q-Tip ve Don Jazzy üstlendi.[1] İlk söylentilere göre, Bruno Mars vokallerinin de yer aldığı şarkı, albümün çıkış singleı olacaktı.[2][3] Ancak Mars şarkıda yer almadı ve şarkı da 23 Ağustos 2011de radyolara servis edildi.[4][5][6]. Barok yaylıların kullanıldığı bir pop şarkısı olan "Lift Off"un nakaratını Beyoncé seslendirmektedir.[7][8][9] Altyapısında synthesizer, bando davulu ve korno da kullanılmaktadır.[10] "Lift Off", olumlu yorumlarla karşılandı. Özellikle nakaratı ve Beyoncénin vokalleri beğeni topladı. Şarkı, Amerikan Billboard Bubbling Under Hot 100 Singles listesinde 21 numaraya yükselirken,[11] Güney ...
Parmigiani RB, Magalhães GS, Galante PA, et al. (2005). "A novel human G protein-coupled receptor is over-expressed in prostate cancer". Genet. Mol. Res. 3 (4): 521-31. PMID 15688318 ...
Beta adrenergic receptor kinase pathway G Proteins. PDB-101. Reece J, Campbell N (2002). Biology. San Francisco: Benjamin ... Sodeman W, Sodeman T (2005). "Physiologic- and Adenylate Cyclase-Coupled Beta-Adrenergic Receptors". Sodeman's Pathologic ... Neve, Kim A.; Seamans, Jeremy K.; Trantham-Davidson, Heather (August 2004). "Dopamine receptor signaling". Journal of Receptor ... Isoforms II, IV and IX are stimulated by beta gamma subunits of the G protein. Isoforms I, V and VI are most clearly inhibited ...
... 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 ...
... 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.[63] ... "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 ...
"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 Res. 15 (17): 7179-80. doi:10.1093/nar/15.17.7179. ... "Pleckstrin homology domain of G protein-coupled receptor kinase-2 binds to PKC and affects the activity of PKC kinase". World J ...
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 ...
"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 (Oct 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 ...
... elevates the intracellular cAMP concentration via beta-adrenergic receptors and activates the cAMP-dependent protein kinase A ( ... "Melatonin receptors , G protein-coupled receptors , IUPHAR/BPS Guide to Pharmacology". www.guidetopharmacology.org. Retrieved ... Many of its biological effects in animals are produced through activation of melatonin receptors, while others are due to its ... Any positive immunological effect is thought to be the result of melatonin acting on high-affinity receptors (MT1 and MT2) ...
... 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 ...
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- ...
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 ...
... 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 ...
Ser/Thr protein kinases such as the Akt/Rac family, the beta-adrenergic receptor kinases, the mu isoform of PKC and the ... Wang, D. S.; Shaw, R.; Winkelmann, J. C.; Shaw, G. (1994). "Binding of PH Domains of β-Adrenergic-Receptor Kinase and β- ... Tyrosine protein kinases belonging to the Btk/Itk/Tec subfamily. Insulin receptor substrate 1 (IRS-1). Regulators of small G- ... Ceramide kinase, a lipid kinase that phosphorylates ceramides to ceramide-1-phosphate. Spectrin/pleckstrin-like InterPro: ...
... beta-adrenergic receptor-coupled adenylate cyclase, and cAMP-dependent protein kinase activities of cardiac sarcolemmal ...
"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 ...
Insulin has an antagonistic effect to epinephrine signaling via the beta-adrenergic receptor (G-Protein coupled receptor). When ... This latter enzyme is itself activated by protein kinase A and deactivated by phosphoprotein phosphatase-1. Protein kinase A ... Glycogen phosphorylase is converted from its less active "b" form to an active "a" form by the enzyme phosphorylase kinase. ... This inhibition is achieved by a similar mechanism, as protein kinase A acts to phosphorylate the enzyme, which lowers activity ...
... 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 ...
"Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel ... "A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent ... Helps NR, Luo X, Barker HM, Cohen PT (2001). "NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to ... Schillace RV, Scott JD (March 1999). "Association of the type 1 protein phosphatase PP1 with the A-kinase anchoring protein ...
... casein kinase iepsilon MeSH D12.776.476.200.125.500 -- beta-adrenergic receptor kinase MeSH D12.776.476.250.067.249 -- cdc2 ... tnf receptor-associated factor 1 MeSH D12.776.476.024.500.750 -- tnf receptor-associated factor 2 MeSH D12.776.476.024.500.875 ... tnf receptor-associated factor 3 MeSH D12.776.476.024.500.937 -- tnf receptor-associated factor 5 MeSH D12.776.476.024.500.968 ... cdc28 protein kinase, s cerevisiae MeSH D12.776.476.250.067.875 -- cyclin-dependent kinase 5 MeSH D12.776.476.250.067.900 -- ...
... it is regulated by Beta adrenergic receptor kinase type 1 (βARK or BARK) also called G protein coupled receptor kinase 2 (GRK2 ... concluded that there are light sensing receptors, melanopsin receptors, are present in blood vessels and mediate wavelength ... but not cGMP-dependent protein kinase or Protein Kinase G (PKG). Furthermore, ... and involves vascular hyperpolarization and this receptor pathway could be targeted for wavelength-specific light-based therapy ...
... 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 ... 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 ...
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 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 ...
"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 (also referred to as βARK or BARK) is a serine/threonine intracellular kinase. It is activated ... Beta adrenergic receptor kinase has been shown to interact with: Beta-gamma complex, G protein GIT1, GNAQ, PDE6G, PRKCB1 and ...
... 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 2.7.11.15) is an enzyme that catalyzes the chemical reaction: ATP + [beta-adrenergic ...
Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the ... Beta-adrenergic receptor kinase 2 (beta-ARK-2) also known as G-protein-coupled receptor kinase 3 (GRK3) is an enzyme that in ... The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G ... and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family". J. Biol. Chem. ...
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. ...
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 ...
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 ...
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: 2.7.11.15. ... 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 ...
Beta-adrenergic receptor kinase 2. HUMAN. 688. UniRef100_P35626. G protein-coupled receptor kinase. PANTR ... IPR000961 AGC-kinase_C. IPR000239 GPCR_kinase. IPR011009 Kinase-like_dom_sf. IPR011993 PH-like_dom_sf. IPR001849 PH_domain. ... IPR000961 AGC-kinase_C. IPR000239 GPCR_kinase. IPR011009 Kinase-like_dom_sf. IPR011993 PH-like_dom_sf. IPR001849 PH_domain. ... IPR000719 Prot_kinase_dom. IPR017441 Protein_kinase_ATP_BS. IPR016137 RGS. IPR036305 RGS_sf. IPR008271 Ser/Thr_kinase_AS. ...
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 ...
In brain and heart PKA increases the activity of the L-type Ca2+ channel Cav1.2 in response to beta-adrenergic stimulation. ... Cav1.2 forms a complex with the beta2-adrenergic receptor, the trimeric GS protein, adenyl … ... The cAMP-dependent protein kinase (PKA) regulates a wide array of cellular functions. ... In brain and heart PKA increases the activity of the L-type Ca2+ channel Cav1.2 in response to beta-adrenergic stimulation. ...
Receptors, Adrenergic, beta / drug effects*. Receptors, Histamine / drug effects. Tyramine / antagonists & inhibitors. ... Creatine Kinase / metabolism. Fibrinolytic Agents / pharmacology*. Histamine / pharmacology. Isoproterenol / antagonists & ... 0/Fibrinolytic Agents; 0/Polydeoxyribonucleotides; 0/Receptors, Adrenergic, beta; 0/Receptors, Histamine; 438HCF2X0M/ ... Furthermore, defibrotide prevents the decline of beta-adrenergic receptor function, a phenomenon related to excessive ...
... beta-adrenergic-receptor kinase [EC:2.7.11.15] K00910 ADRBK; beta-adrenergic-receptor kinase [EC:2.7.11.15] 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 ...
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+ ...
... regulator of G-protein signaling homology domain of G protein-coupled receptor kinases 5 and 6 in beta 2-adrenergic receptor ... Protein-Coupled Receptor Kinases 5 and 6 in β2-Adrenergic Receptor and Rhodopsin Phosphorylation ... Protein-Coupled Receptor Kinases 5 and 6 in β2-Adrenergic Receptor and Rhodopsin Phosphorylation ... Protein-Coupled Receptor Kinases 5 and 6 in β2-Adrenergic Receptor and Rhodopsin Phosphorylation ...
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, ...
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- ...
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 ...
2005) Protein kinase activity of phosphoinositide 3-kinase regulates beta-adrenergic receptor endocytosis. Nat Cell Biol 7:785- ... 2001) Agonist-dependent recruitment of phosphoinositide 3-kinase to the membrane by beta-adrenergic receptor kinase 1. A role ... 2002) Phosphoinositide 3-kinase regulates beta2-adrenergic receptor endocytosis by AP-2 recruitment to the receptor/beta- ... Among the most significant are chemokine receptors, β-adrenergic receptors, and angiotensin II AT1 receptors (13-16). ...
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. ...
  • 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)
  • The BEK/FGFR-2 receptor is a membrane-spanning tyrosine kinase with the typical features of FGF receptors. (duke.edu)
  • A critical component of environment-sensing is plasma membrane-localized receptors. (frontiersin.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)
  • It has structural similarity to the membrane-associated guanylate kinase homologue (MAGUK) family. (wikipedia.org)
  • Fatty acids cause the following signaling cascade: Sympathetic nervous system terminals release Norepinephrine onto a Beta-3 adrenergic receptor on the plasma membrane. (wikipedia.org)
  • After being sequestered, the affected receptors can either be degraded by lysosomes or reinserted into the plasma membrane, which is called receptor recycling. (wikipedia.org)
  • PSD-95 is a member of the membrane-associated guanylate kinase (MAGUK) family. (wikipedia.org)
  • Within a cell, D5 receptors are found on the membrane of soma and proximal dendrites. (wikipedia.org)
  • In the neuron, making sense of neurotransmitter activity requires specific receptors to be located in the lipid membrane at the synapse. (wikipedia.org)
  • Subsequently, the receptor could be either directed to degradation compartments (lysosomes) or recycled back to the plasma membrane where it can again signal. (wikipedia.org)
  • Studies utilizing PHPLCδ1 domain over-expression (acting as PI(4,5)P2 buffer or blocker) , PIPKIγ knockout in chromaffin cell and in central nerve system , PIPKIγ knockdown in beta cell lines , and over-expression of membrane-tethered inositol 5-phosphatase domain of synaptojanin 1 , all suggested vesicle (synaptic vesicle and LDCV) secretion were severely impaired after PI(4,5)P2 depletion or blockage. (wikipedia.org)
  • PtdIns(4,5)P2 is a substrate for hydrolysis by phospholipase C (PLC), a membrane-bound enzyme activated through protein receptors such as α1 adrenergic receptors. (wikipedia.org)
  • As such, its effects do not rely on the cognate membrane receptors. (wikipedia.org)
  • citation needed] The 5-HT receptors, the receptors for serotonin, are located on the cell membrane of nerve cells and other cell types in animals, and mediate the effects of serotonin as the endogenous ligand and of a broad range of pharmaceutical and hallucinogenic drugs. (wikipedia.org)
  • A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastoma. (nih.gov)
  • Src kinase-dependent epidermal growth factor receptor transactivation in PPARgamma ligand-induced suppression of Porphyromonas gingivalis interference with salivary mucin synthesis. (nih.gov)
  • Growth factors and their receptors coordinate neuronal differentiation during development, yet their roles in the embyronal tumor neuroblastoma, where differentiation is a validated treatment strategy, remain unclear. (duke.edu)
  • Protein kinases are implicated in neuronal cell functions such as modulation of ion channel function, trafficking, and synaptic excitability. (frontiersin.org)
  • Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress. (wikipedia.org)
  • Neuregulin is involved in the "switching" of oligodendrocytes from the mode of myelination that is independent of neuronal activity to the mode that is dependent upon glutamate binding to NMDA receptors. (wikipedia.org)
  • This encoded protein is characterized by two WW domains, a guanylate kinase-like domain, and multiple PDZ domains. (wikipedia.org)
  • These kinases are a family of signaling molecules expressed at various submembrane domains and contain the PDZ, SH3 and the guanylate kinase domains. (wikipedia.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)
  • PIP2 functions as an intermediate in the [IP3/DAG pathway], which is initiated by ligands binding to G protein-coupled receptors activating the Gq alpha subunit. (wikipedia.org)
  • This receptor protein has a large, extracellular binding domain which will bind its respective ligands (e.g. neurotransmitters and hormones). (wikipedia.org)
  • Recent work indicates that exogenous ligands that activate the δ receptors mimic the phenomenon known as ischemic preconditioning. (wikipedia.org)
  • In June of that year, Raymond Ahlquist, Professor of Pharmacology at Medical College of Georgia, published a paper concerning adrenergic nervous transmission. (wikipedia.org)
  • In 1954, he was able to incorporate his findings in a textbook, Drill's Pharmacology in Medicine, and thereby promulgate the role played by α and β receptor sites in the adrenaline/noradrenaline cellular mechanism. (wikipedia.org)