2.7.11.15 ATP + a protein - 2.7.11.15 ATP + alpha-synuclein colocalization of GRK2, GRK5, alpha-synuclein, and tau in neurodegenerative disorders characterized by fibrillary tau inclusions and/or alpha-synuclein-enriched Lewy bodies, overview 2.7.11.15 ATP + alpha1 beta-adrenergic receptor substrate specificities of GRK2 and GRK3 in cardiac myocytes, overview 2.7.11.15 ATP + alpha1-adrenergic receptor - 2.7.11.15 ATP + alpha1D-adrenergic receptor inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances alpha1D-adrenergic receptor constriction and signalling, overview 2.7.11.15 ATP + alpha2A-adrenergic receptor - 2.7.11.15 ATP + angiotensin receptor phosphorylation by GRK2 preceeds the binding of arrestins, which inhibits the seven-transmembrane receptor, but initiates internalization, overview 2.7.11.15 ATP + beta-adrenergic receptor - 2.7.11.15 ATP + beta-adrenergic receptor general role in the desensitization of synaptic receptors 2.7.11.15 ATP + beta-adrenergic receptor specifically phosphorylates and inactivates beta-AR after stimulation by receptor agonists, facilitating the binding of the inhibitor protein beta-arrestin to the receptor, during myocardial ischemia the membrane activity of beta-ARK is increased 2.7.11.15 ATP + beta-adrenergic receptor beta-ARK 1 might be involved in uncoupling and down-regulation of beta-AR, presumably both beta1- and beta2-AR, in failing hearts via receptor phosphorylation 2.7.11.15 ATP + beta-adrenergic receptor presumably modulates some receptor-mediated immune functions 2.7.11.15 ATP + beta-adrenergic receptor role of beta-ARK 1 in heart failure, myocardial development and function 2.7.11.15 ATP + beta-adrenergic receptor natural substrate: beta2-adrenergic receptor 2.7.11.15 ATP + beta-adrenergic receptor beta-ARK 1 and 2 may have a similar substrate specificity in vivo 2.7.11.15 ATP + beta-adrenergic receptor regulation of the beta-AR function in vivo 2.7.11.15 ATP + beta-adrenergic receptor desensitization of beta-adrenergic receptor 2.7.11.15 ATP + beta-adrenergic receptor plays, together with cAMP-dependent protein kinase, an important role in agonist-promoted receptor desensitization, coordinated regulatory mechanism involving sequential depalmitoylation and phosphorylation of the beta2-AR by the two kinases 2.7.11.15 ATP + beta-adrenergic receptor agonist-occupied form of the receptor 2.7.11.15 ATP + beta-adrenergic receptor involved in homologous desensitization of beta-adrenergic receptor 2.7.11.15 ATP + beta-adrenergic receptor functional role of the beta-ARK/beta-arrestin mechanism of receptor desensitization in immune cells 2.7.11.15 ATP + beta-adrenergic receptor agonist-activated receptor substrate 2.7.11.15 ATP + beta-adrenergic receptor betaARK is involved in myocardial beta-adrenergic receptor signaling, enzyme dysfunction can cause heart failure, regulation mechanism and physiology, overview 2.7.11.15 ATP + beta-adrenergic receptor betaARK1 is responsible for desensitization and down regulation of beta-adrenergic receptors 2.7.11.15 ATP + beta-adrenergic receptor desensitization of the receptor by GRK2 and GRK3 2.7.11.15 ATP + beta-adrenergic receptor G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis via clathrin-coated pits 2.7.11.15 ATP + beta-adrenergic receptor G-protein-coupled receptor kinase-2 and beta-arrestin-2 are involved in exercise-induced beta-adrenergic receptor trafficking from cytosol to membranes in adipocytes, role in beta-adrenergic receptor-ubiquitination in the ubiquitin-proteasome pathway 2.7.11.15 ATP + beta-adrenergic receptor GRK3 and GRK2 are involved in down-regulation of the alpha2B-adrenoceptor, regulation of the pathway, overview 2.7.11.15 ATP + beta-adrenergic receptor in human heart failure, impaired beta-adrenergic receptor signaling compromises cardiac sensitivity to inotropic stimulation, overview 2.7.11.15 ATP + beta-adrenergic receptor phosphorylation and internalization of the receptor requires clathrin, GRK2 specifically phosphorylates the activated form of the receptor that promotes the translocation of beta-arrestins to the plasma membrane, overview 2.7.11.15 ATP + beta-adrenergic receptor phosphorylation by GRK2 preceeds the binding of arrestins, which inhibits the seven-transmembrane receptor, but initiates internalization, overview 2.7.11.15 ATP + beta-adrenergic receptor the enzyme is involved in regulation of the beta-adrenergic receptor signaling by inhibiting arrestin recruitment to the receptor and subsequent desensitization and internalization, regulation of GRK2 by S-nitrosylation, molecular mechanism, overview 2.7.11.15 ATP + beta-adrenergic receptor the mechanism of myocardial beta-adrenergic receptor desensitization during cardiac surgery involves GRK2, overview 2.7.11.15 ATP + beta1-adrenergic receptor - 2.7.11.15 ATP + beta2-adrenergic receptor - 2.7.11.15 ATP + beta2-adrenergic receptor desensitization of the receptor with subsequent decline in the stimulatory effects of beta2-adrenergic agonists over time, the receptor is involved in alveolar Na+ and water clearance 2.7.11.15 ATP + beta2-adrenergic receptor role of GRK activity in the regulation of beta2 adrenergic signaling, feedback mechanism, overview 2.7.11.15 ATP + calcium-sensing receptor homologous desensitization of G protein-coupled receptors is generally mediated by GRKs through phosphorylation-dependent and independent mechanisms, GRK2 can phosphorylate calcium-sensing receptor and, along with beta-arrestins, can attenuate calcium-sensing receptor-mediated signaling, mechanism, overview 2.7.11.15 ATP + corticotropin-releasing factor receptor type 1 i.e. CRFR1, phosphorylation leads to desensitization and downregulation of the receptor 2.7.11.15 ATP + dopamine D1 receptor phosphorylation by GRK2 has a regulatory role as part of the PI3K-PKC-GRK2 cascade 2.7.11.15 ATP + dopamine D3 receptor the receptor is activated by GRK2 and GRK3 phosphorylation involving beta-arrestins, GRK-mediated regulation of receptor-filamin complex stability and receptor-G protein signaling potential, GRK2 reduces the dopamine D3 receptor signaling, overview 2.7.11.15 ATP + DREAM i.e. downstream regulatory element antagonist modulator protein, GRK2 mediates phosphorylation of DREAM/potassium channel interacting protein KChIP3, a multifunctional protein of the neuronal calcium sensor subfamily of Ca2+-binding proteins with specific roles in different cell compartments, regulating membrane trafficking of Kv4.2 potassium channel, phosphorylation of Ser95 affects cell surface localization, but not Kv4 channel tetramerization, overview 2.7.11.15 ATP + epithelial Na+ channel channel inactivation 2.7.11.15 ATP + ezrin phosphorylation of ezrin affects the 7TM receptor mediated cytoskeletal reorganization 2.7.11.15 ATP + G protein-coupled receptor - 2.7.11.15 ATP + G protein-coupled receptor desensitization by GRK2 of the ligand-activated receptor 2.7.11.15 ATP + G protein-coupled receptor desensitization of agonist-activated receptor 2.7.11.15 ATP + G protein-coupled receptor GRK2 performs desensitization of the ligand-activated receptor by phosphorylation 2.7.11.15 ATP + G protein-coupled receptor phosphorylation has a regulatory role, regulation of the signal transduction involving GRK2 and beta-arrestin, overview 2.7.11.15 ATP + G protein-coupled receptor regulation mechanism of GRK2, overview, regulation by phosphorylation at specific sites via distinct specific kinases, overview 2.7.11.15 ATP + insulin receptor substrate 1 role of GRK2 in insulin receptor IR signaling 2.7.11.15 ATP + insulin receptor substrate-1 - 2.7.11.15 ATP + M1 muscarinic acetylcholine receptor phosphorylation-dependent and -independent mechanisms in the regulation of M1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 in hippocampal neurons, GRK2 can inhibit the receptor-dependent signaling via phospholipase C, overview 2.7.11.15 ATP + Nedd4 GRK2 interacts with and phosphorylates the ubiquitin protein ligase Nedd4 preventing the binding to proline-rich motifs present in the C-termini of epithelial Na+ channel subunits and inhibition of the channels, overview 2.7.11.15 ATP + Nedd4-2 GRK2 interacts with and phosphorylates the ubiquitin protein ligase Nedd4-2 preventing the binding to proline-rich motifs present in the C-termini of epithelial Na+ channel subunits and inhibition of the channels, overview 2.7.11.15 ATP + p38 MAP kinase GRK2 inactivates and regulates MAP kinase p38 modulating p38-dependent physiological processes, p38 and GRK2 are localized in a multimolecular complex 2.7.11.15 ATP + PDEgamma phosphorylation of PDEgamma possibly stimulates EGFR-mediated ERK activation 2.7.11.15 ATP + PDGFRbeta - 2.7.11.15 ATP + phosducin phosducin is activated to inhibit Gbetagamma protein 2.7.11.15 ATP + platelet-derived growth factor receptor-beta feedback inhibition mechanism, overview 2.7.11.15 ATP + protein specifically phosphorylates the agonist-occupied forms of the beta 2-adrenergic receptor and related G protein-coupled receptors 2.7.11.15 ATP + protein the enzyme mediates agonist-dependent phosphorylation of the beta 2-adrenergic and related G protein-coupled receptors 2.7.11.15 ATP + protein specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors 2.7.11.15 ATP + protein M33 GRK2 is a potent regulator of the mouse cytomegalovirus GPCR protein M33-induced Gq/11 signaling through its ability to phosphorylate M33 and sequester Galphaq/11 proteins dependent on an intact RH domain, the protein M33 is able to induce inositol phosphate accumulation, activate NF-kappaB, and promote smooth muscle cell migration, viral GPCRs like M33 play a role in viral dissemination in vivo, M33 is required for efficient murine cytomegalovirus replication in the mouse, and induces several signlaing pathways, overview 2.7.11.15 ATP + rhodopsin - 2.7.11.15 ATP + rhodopsin light-activated rhodopsin 2.7.11.15 ATP + ribosomal protein P2 activation of P2 2.7.11.15 ATP + Smo GPRK2 participates in Hedgehog signaling in Drosophila melanogaster, and plays a key role in the Smo signal transduction pathway, when Gprk2 levels are lowered, Smo still accumulates at the cell membrane, but its activation is reduced, overview 2.7.11.15 ATP + Smoothened protein GRK2 promotes smoothened signal transduction involved in regulation of cellular proliferation and differentiation through activation of the transcription factor Gli, overview 2.7.11.15 ATP + synuclein - 2.7.11.15 ATP + [beta-adrenergic receptor] - 2.7.11.15 ATP + [beta2-adrenergic receptor] - 2.7.11.15 ATP + [delta opioid receptor] - 2.7.11.15 ATP + [neurotensin receptor] the enzyme phosphorylates only the C-terminal serine residues 2.7.11.15 ATP + [TSH receptor] GRK2 and GRK3, receptor activation 2.7.11.15 ezrin + ATP - 2.7.11.15 histamine H2 receptor + ATP - 2.7.11.15 moesin + ATP - 2.7.11.15 additional information enzyme is important in mediating rapid agonist-specific desensitization 2.7.11.15 additional information role for beta ARK in modulating some receptor-mediated immune functions 2.7.11.15 additional information general role in the desensitization of synaptic receptors 2.7.11.15 additional information Gprk2 is required for egg morphogenesis 2.7.11.15 additional information beta-ARK is probably a general adenylate cyclase-coupled receptor kinase 2.7.11.15 additional information beta-ARK 1 is a key regulatory enzyme involved in the regulation of G protein-coupled receptors which associate with microsomal and plasma membranes 2.7.11.15 additional information plays a pivotal role in phosphorylating and desensitizing G protein-coupled receptors by vitue of pleckstrin homology domain-mediated membrane translocation 2.7.11.15 additional information beta-ARK activity is regulated by endogenous G proteins in different intracellular locations 2.7.11.15 additional information phosphorylates and regulates receptors coupled to either stimulation or inhibition of adenylate cyclase 2.7.11.15 additional information general function in desensitizing of many G protein-coupled receptor systems 2.7.11.15 additional information involved in the regulation of G protein-coupled receptor function, beta-ARK 1 appears to be the predominant GRK in early embryogenesis and plays a fundamental role in cardiac development, enzyme participates in intracellular signal transduction mechanisms, which regulate cardiogenesis 2.7.11.15 additional information adenovirus-mediated overexpression of phosphoinositide 3-kinase restore contractile function of cardiac myocytes isolated from failing hearts, the recombinant PIK replaces the endogenous PIK in the transgenic pigs, the endogenous PIK shows abnormally increased activity in complex with betaARK1, overview 2.7.11.15 additional information betaARK enhances the contractility in heart myocardium via inhibition of Gbetagamma subunits 2.7.11.15 additional information betaARK1 binds phosphoinositide 3-kinase, which is by this way targeted to agonist-stimulated beta-adrenergic receptors, where it regulates endocytosis, disruption of the betaARK1-PIK complex leads to restoration of beta-adrenergic receptor signaling and contractile function in heart failure, overview 2.7.11.15 additional information betaARK1 inhibition improves beta-adrenergic signaling and contractile function in failing human myocytes 2.7.11.15 additional information brain death induction, as well as sham-operation of pigs, lead to uncoupling of the beta-adrenergic receptor with acutely increased myocardial beta-adrenergic receptor kinase activity leading to left ventricular dysfunction 2.7.11.15 additional information dopamine D3 receptor binds to G proteins, the coupling is regulated by the filamin expression level 2.7.11.15 additional information G protein-coupled receptors are involved in the regulation of diverse physiological processes, mechanisms of G protein-coupled receptor desensitization, e.g. by phosphorylation or feedback inhibition, overview 2.7.11.15 additional information GRK2 and GRK3 are involved in methacholine-stimulated inositol 3-phosphate production 2.7.11.15 additional information GRK2 expression plays a role in the fly development, GRK2 expression is required in the germline for proper formation of the anterior egg structures, egg hatching, and for early and late embryogenesis 2.7.11.15 additional information GRK2 is involved in A2 adenosine receptor response to agonists 2.7.11.15 additional information GRK2 mediates endothelin-1-induced insulin resistance via the inhibition of both Galphaq/11 and insulin receptor substrate-1 pathways in 3T3-L1 adipocytes, GRK2 does not affect insulin receptor tyrosine phosphorylation 2.7.11.15 additional information GRK2 regulation mechanism of ERK activation involving interaction with mitogen-activated protein kinase, GRK2 diminishes the level of activating phosphorylation of ERK by CCL2 binding to chemokine receptor CCR2 in endothelial cells 2.7.11.15 additional information GRK3 is essential for induction of germinal vesicle breakdown, GRK3 forms a complex with beta-arrestin-2 causing G protein-coupled receptor desensitization 2.7.11.15 additional information GRKs are involved in diverse physiological processes and pathologies, overview 2.7.11.15 additional information phosphorylation of heptahelical receptors by GRK2 is a universal regulatory mehanism leading to desensitization of G protein signaling and to the activation of alternative signaling pathways 2.7.11.15 additional information the enzyme is involved in G protein-coupled receptor signal transduction pathways and desensitization, GRK2 is a multiple domain kinase regulating by multiple mechanisms, overview 2.7.11.15 additional information adrenal GRK2 upregulation mediates sympathetic overdrive in heart failure, adrenal gland-specific GRK2 inhibition reverses alpha2 beta-adrenergic receptor dysregulation in heart failure, resulting in lowered plasma catecholamine levels, improved cardiac beta-adrenergic signaling and function, and increased sympatholytic efficacy of a alpha2 beta-adrenergic agonist 2.7.11.15 additional information GPCR-dependent kinases play a major role in agonist-induced phosphorylation and desensitization of G-protein coupled receptors, GRK2 is a component of neuronal and glial fibrillary tau deposits with no preference in tau isoform binding, GRK2 may play a role in hyperphosphorylation of tau in tauopathies 2.7.11.15 additional information GRK activity is regulated by phosphorylation through several kinases and by interactions with several cellular proteins, e.g. calmodulin, caveolin or RKIP, GRK also interacts with PI3K, Akt, GIT or MEK, the interactions occur at the RH and PH domains, overview, the GRK interactome: role of GRKs in GPCR regulation and signaling, detailed overview 2.7.11.15 additional information GRK-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling and desensitization, beta-arrestin-mediated receptor internalization, activity of GRKs and subcellular targeting is tightly regulated by interaction with receptor domains, G protein subunits, lipids, anchoring proteins and calcium-sensitive proteins, selective binding of activated Galphaq and Galpha-11 to RH domains of GRK2 and GRK3 selectively inhibits Gq signaling 2.7.11.15 additional information GRK2 activity leads to translocation of parts of beta-adrenergic receptors to endocytic vesicles 2.7.11.15 additional information GRK2 interacts with multiple signaling proteins and is involved in several cellular processes, e.g. expression and regulation of key cardiac seven-transmembrane receptors, 7TM receptors, such as the beta-adrenergic and angiotensin receptors, GRK2 interacts with NCS-1, mechanism, overview, GRK2 inhibition can ameliorate heart failure, molecular mechanism of GRK2 activity regulation, GRK2 is probably involved in regulation of hypertension, overview 2.7.11.15 additional information GRK2 is essential, and GRK2-deficient mice are embryonically lethal 2.7.11.15 additional information GRK2 negatively regulates glycogen synthesis in mouse liver FL83B cells, regulates basal and insulin-stimulated glycogen synthesis via a post-IR signaling mechanism, and GRK2 may contribute to reduced IR expression and function during chronic insulin exposure 2.7.11.15 additional information GRK2 plays a role in sodium transport regulation and is involved in the development of essential hypertension, overview 2.7.11.15 additional information GRK2 regulates 7TM G-protein-coupled receptor activity, GRK2 promotes the association between active Smoothened and beta-arrestin 2, overview 2.7.11.15 additional information insulin-mediated dopamine D1 receptor desensitization and underlying molecular mechanism in opossum kidney cells, overview 2.7.11.15 additional information G protein-coupled receptor kinases and arrestins are key participants in the canonical pathways leading to phosphorylation-dependent G protein-coupled receptor, GPCR, desensitization, endocytosis, intracellular trafficking and resensitization as well as in the modulation of important intracellular signaling cascades by GPCR, structure-function relationships, overview. GRK activity is tightly modulated by mechanisms including phosphorylation by different kinases and interaction with several cellular proteins such as calmodulin, caveolin or RKIP. Different mechanisms of signalling pathways modulation by GRK2, and regulation of GRK2, overview 2.7.11.15 additional information G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview 2.7.11.15 additional information Gprk2, a Drosophila member of the G protein-coupled receptor kinases, plays a key role in the Smo, i.e. Smoothened, signal transduction pathway, overview. When Gprk2 levels are lowered, Smo still accumulates at the cell membrane, but its activation is reduced. Regulation of Gprk2 expression by Hh signaling in the wing disc, but Gprk2 is also required for Hh signaling in the wing disc, overview 2.7.11.15 additional information GRK-mediated desensitization of beta2-adrenergic receptors is sufficient to cause declines in cAMP signals. GRK-mediated desensitization is primarily responsible for a sustained suppression of beta2AR signaling, overview 2.7.11.15 additional information GRK2 causes enhanced catecholamine secretion by desensitizing sympatho-inhibitory alpha2-adrenergic receptors of chromaffin cells and thereby aggravating heart failure 2.7.11.15 additional information GRK2 in cardiac myocytes catalyzes phosphorylation and desensitization of different G protein-coupled receptors through specificity controlled by their carboxyl-terminal pleckstrin homology domain, overview 2.7.11.15 additional information GRK2 is important for myocardial regulation, and is up-regulated in the dysfunctional heart 2.7.11.15 additional information GRK2 substrate specificity in adult rat cardiac myocytes, overview. GRK2 completely lacks the capacity to attenuate phenylephrine-stimulated IP generation 2.7.11.15 additional information GRK3 in cardiac myocytes catalyzes phosphorylation and desensitization of different G protein-coupled receptors through specificity controlled by its carboxyl-terminal pleckstrin homology domain. GRK3 controls cardiac alpha1-adrenergic receptor responsiveness, distinct functions of GRK3 in regulation of cardiac contractility and growth, overview 2.7.11.15 additional information GRK3 substrate specificity in adult rat cardiac myocytes, overview 2.7.11.15 additional information carboxyl-terminus of GRK2 interacts with Hsp90. Reactive oxygen species (ROS)-mediated mitochrondrial localisation of GRK2 is dependent on Hsp90 binding 2.7.11.15 additional information Gprk2 interacts with the Drosophila IkB homolog Cactus 2.7.11.15 additional information GRK2 interacts with Hsp90. Reactive oxygen species (ROS)-mediated mitochrondrial localisation of GRK2 is dependent on Hsp90 binding 2.7.11.15 additional information RhoAGTP is a binding partner for enzyme GRK2 2.7.11.15 radixin + ATP -