2.7.11.16 ATP + a G protein-coupled receptor the GRKs are important in the cardiovascular system, the major G protein-coupled receptor regulatory pathway involves phosphorylation of activated receptors by GRKs, followed by binding of arrestin proteins, which prevent receptors from activating downstream heterotrimeric G protein pathways while allowing activation of arrestin-dependent signaling pathways, general mechanisms of GRK-arrestin regulation, overview, physiological functions and potential pathophysiological roles of GRKs and arrestins in human disorders, overview 2.7.11.16 ATP + alpha-synuclein GRK5 phosphorylates Ser-129 of alpha-synuclein at the plasma membrane and induces translocation of phosphorylated alpha-synuclein to the perikaryal area, GRK5 promotes alpha-linolenic acid-induced oligomerization of alpha-synuclein, alpha-synuclein phosphorylation by GRK5 plays a crucial role in the pathogenesis of sporadic Parkinson's disease, sPD 2.7.11.16 ATP + ATP + G protein-coupled receptor - 2.7.11.16 ATP + beta-adrenergic receptor desensitization of the receptor by GRK4, GRK5, and GRK6 2.7.11.16 ATP + BLT1 receptor GRK6, ablation of GRK6 leads to augmented signaling by leukotriene B4 acting through the BLT1 receptor 2.7.11.16 ATP + central M2 muscarinic receptor desensitization of the receptor by GRK5, GRK5 regulates pulmmonary responses by activation of the airway receptor, but does not regulate the peripheral cardiac muscarinic receptors 2.7.11.16 ATP + CXCR4 receptor GRK6, the pathway is important in facilitating neutrophil retention in the bone marrow 2.7.11.16 ATP + dopamine D1 receptor rapid desensitization of the receptor by GRK4 and GRK6, Na+/H+ exchanger activity of the receptor, overview 2.7.11.16 ATP + dopamine D1 receptor dopamine D1 receptors in IEC-6 rapidly desensitize to D1-like agonist stimulation and GRK 6 isozymes A and B, but not GRK 4, appear to be involved in agonist-mediated responsiveness and desensitization 2.7.11.16 ATP + dopamine D1 receptor GRK4 2.7.11.16 ATP + G protein-coupled receptor phosphorylation has a regulatory role 2.7.11.16 ATP + G protein-coupled receptor regulation mechanism of GRK5, overview, regulation by phosphorylation at specific sites via distinct specific kinases, overview 2.7.11.16 ATP + G-protein-coupled receptor leading to receptor endocytosis 2.7.11.16 ATP + moesin phosphorylation at Thr66 2.7.11.16 ATP + protein p105 - 2.7.11.16 ATP + rhodopsin - 2.7.11.16 ATP + [alpha-synuclein] the enzyme phosphorylates alpha-synuclein at Ser129 2.7.11.16 ATP + [beta2-adrenergic receptor] GRK5 plays a distinctive role in the phosphorylation of the beta2AR 2.7.11.16 ATP + [dopamine D1 receptor] GRK4 constitutively phosphorylates active and inactive receptor, in the latter case diminishing stimulation of the receptor by dopamine, phosphorylation reduces receptor desensitization and internalization, followed by reduced cAMP accumulation 2.7.11.16 ATP + [G protein-coupled receptor] - 2.7.11.16 ATP + [G protein-coupled receptor] GRK4-6 2.7.11.16 ATP + [G-protein-coupled receptor] - 2.7.11.16 ATP + [G-protein-coupled receptor] GRK5 effectively phosphorylates inactive forms of several G-protein-coupled receptors, including serotonin 5-HT2C, beta2-adrenergic and M2 muscarinic receptors and rhodopsin 2.7.11.16 ATP + [M3 muscarinic acetylcholine receptor] GRK6 plays a major role in specific M3 muscarinic acetylcholine receptor regulation 2.7.11.16 ATP + [TSH receptor] GRK4-6, receptor activation 2.7.11.16 additional information enzyme is involved in fertilization 2.7.11.16 additional information enzyme mainly involved in homologous desensitization of the TSH receptor 2.7.11.16 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 2.7.11.16 additional information GRK5 and especially GRK6 have selective regulatory roles in cAMP accumulation response of the secretin receptor to agonists like beta-arrestin-1 or forskolin, overview 2.7.11.16 additional information GRK5 defects can cause obstructive airway diseases such as asthma 2.7.11.16 additional information GRK5 elevates blood pressure in vascular smooth muscle via Gi signaling involing the beta1-adrenergic receptor, mechanism overview 2.7.11.16 additional information GRKs are involved in diverse physiological processes and pathologies, overview 2.7.11.16 additional information the enzyme is involved in GPCR signal transduction pathways and desensitization 2.7.11.16 additional information the GRK4 isozymes are differentially regulated, overview 2.7.11.16 additional information the GRK4-6 family member enzymes mediate beta-adrenergic receptor desensitization, the beta-adrenergic receptor is stimulated by agonists such as isoproterenol, cholera toxin, or forskolin, and induces cAMP production 2.7.11.16 additional information the variable C-terminal extension of GRK6 constitutes an accessorial autoregulatory domain 2.7.11.16 additional information arrestin-2 and GRK5, not GRK6, interact with NFkappaB1 p105 and negatively regulate lipopolysaccharide-stimulated ERK1/2 activation in macrophages, overview 2.7.11.16 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 2.7.11.16 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 2.7.11.16 additional information GRK4 is involved in activity of dopamine receptors in renal proximal tubules and mediates sodium reabsorption and blood pressure regulation 2.7.11.16 additional information GRK6 is a key regulator of dopaminergic signaling and lymphocyte chemotaxis 2.7.11.16 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 2.7.11.16 additional information G protein-coupled receptors and Toll-like receptors play a crucial role in the regulation of macrophage biology and innate immunity, overview 2.7.11.16 additional information G protein-coupled receptors are involved in regulating pain signaling in the context of inflammation. G protein-coupled receptor kinases modulate signaling through these receptors, GRK6 controls post-inflammatory visceral hyperalgesia, overview 2.7.11.16 additional information GRK5 is important for myocardial regulation, and is up-regulated in the dysfunctional heart. But GRK5 also is a nuclear a class II histone deacetylase kinase that plays a key role in maladaptive cardiac hypertrophy apparently independent of any action directly on G protein coupled receptors, overview. Chronic Gq signaling results in the translocation of GRK5 to the nucleus, where GRK5 activity plays a role in MEF2 activation, which has implications for induction of hypertrophic gene expression. GRK5 interacts with histone deacetylase kinases in vivo 2.7.11.16 additional information GRK6 plays a role in determining the course of inflammation and controls chronicity and severity of dextran sodium sulphate-induced colitis in mice, overview