Disease relevance of Adrbk1

• Consistently, Western blot analysis of tissue extracts from the nonischemic region of the left ventricle revealed 3.0-, 2.6-, and 1.5-fold elevations of GRK2, GRK5, and beta-arrestin-1, respectively, 7 days after induction of myocardial infarction compared with the sham-operated rats (P < 0.05) [1].
• Myocardial G protein-coupled receptor kinase 2 (GRK2) has been shown to be involved in the pathophysiology of congestive heart failure (CHF) [1].
• Hypoxia/ischemia modulates G protein-coupled receptor kinase 2 and beta-arrestin-1 levels in the neonatal rat brain [2].
• Effect of hypothyroidism on G protein-coupled receptor kinase 2 expression levels in rat liver, lung, and heart [3].
• Subcellular redistribution of GRK2 and GRK5 may be involved in cardiac hypertrophy resulting from chronic hypertension [4].

High impact information on Adrbk1

• Furthermore, GRK2 expression increased in sinusoidal endothelial cells from portal hypertensive rats and knockdown of GRK2 restored Akt phosphorylation and NO production, and normalized portal pressure [5].
• A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension [5].
• beta-Adrenergic receptor kinase (beta ARK) and beta-arrestin function in the homologous or agonist-activated desensitization of G protein-coupled receptors [6].
• Chronic treatment of rats with albuterol also increased cAMP phosphodiesterase activity and G protein-coupled receptor kinase-2, but the extent to which these events contributed to beta(2)-adrenoceptor desensitization was unclear given that forskolin was active in both groups of animals and that desensitization was heterologous [7].
• A beta-adrenergic receptor kinase-like enzyme is involved in olfactory signal termination [8].

Chemical compound and disease context of Adrbk1

• The LY294002 potentiating effects are completely prevented by betaARK-ct, a peptide inhibitor of beta-adrenergic receptor kinase-1 (betaARK1) as well as G(betagamma) signaling, but not by disrupting G(i) function with pertussis toxin [9].
• Ang II-induced ERK activation was abolished by pretreatment with pertussis toxin and by overexpression of the Gbetagamma subunit-binding domain of the beta-adrenergic receptor kinase 1 in cardiac fibroblasts but not in cardiac myocytes [10].
• Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor kinase 1 (betaARK1), which specifically blocks signaling mediated by the betagamma subunits of G proteins, blocked the PGF2alpha-induced activation of MAP kinase [11].
• Rapid agonist-induced beta-adrenergic receptor kinase translocation in C6 glioma cells [12].

Biological context of Adrbk1

• Hypothyroid animals show significant up-regulation ( approximately 50% increase compared with controls) in GRK2 levels in heart and lung at 60 days after birth, whereas a 50% reduction is detected in the liver at this stage [3].
• GnRH-stimulated inositol trisphosphate production by gonadotropes also was inhibited, suggesting a site of action for GRK2 at phospholipase Cbeta or earlier in the signal transduction pathway [13].
• The results suggest different roles for GRK2 and GRK5 in G-protein signaling and RNA biogenesis [4].
• Our data suggest that in cirrhosis-induced vasodilation, the AT1-R is desensitized by GRK-2 and beta-arrestin-2 and that changed patterns of phosphorylated Ca(2+) sensitizing proteins decrease Ca(2+) sensitivity [14].
• Angiotensin receptor blockade improves myocardial beta-adrenergic receptor signaling in postinfarction left ventricular remodeling: a possible link between beta-adrenergic receptor kinase-1 and protein kinase C epsilon isoform [15].

Anatomical context of Adrbk1

• Immunohistochemical analysis of myocardial tissue sections and Western blot analysis of isolated cells revealed localization of GRK2 and beta-arrestin-1 predominantly in endothelial cells [1].
• In addition, we analyzed GRK2 expression in the hippocampus by immunohistochemistry [2].
• The reported changes in GRK2 levels and in the receptor/kinase ratio predict alterations in adrenergic receptor desensitization and signal transduction efficacy consistent with those observed in thyroid disorders, thus suggesting a relevant role for the modulation of GRK2 expression in this physiopathological condition [3].
• We questioned the effect of age on caveolin-1 expression and interaction between caveolin-1 and GRK-2 in vascular smooth muscle (VSM) isolated from 2-, 6-, 12-, and 24-mo-old male Fischer 344 rat aorta [16].
• Myocyte redistribution of GRK2 and GRK5 in hypertensive, heart-failure-prone rats [4].

Associations of Adrbk1 with chemical compounds

• Co-transfection of neurons with either a non-G alpha(q/11)-binding (D110A) GRK2 mutant or the catalytically inactive (D110A,K220R)GRK2 did not suppress acute M1 mACh receptor-stimulated inositol 1,4,5-trisphosphate production [17].
• High efficiency method for gene transfer in normal pituitary gonadotropes: adenoviral-mediated expression of G protein-coupled receptor kinase 2 suppresses luteinizing hormone secretion [13].
• Administration of either lactacystin or propranolol did not alter GRK-2 and beta2-AR protein expressions after exercise [18].
• GRK2 was expressed mainly in the Triton X-100 soluble fraction in the left ventricle with similar expression levels between SHHF and age-matched Wistar-Kyoto (WKY) rats [4].
• The heparin-sensitive kinase may not be GRK2, GRK3, or GRK6 expressed in CHO/AT1A-R cells, since angiotensin II did not induce translocation of these receptor kinases [19].

Co-localisations of Adrbk1

• GRK2 had a striated pattern which colocalized with sarcomeric alpha-actinin and G protein in both SHHF and WKY rat myocytes and specifically accumulated in the intercalated disks of myocytes from SHHF but not WKY rats [4].

Regulatory relationships of Adrbk1

• Similarly, depletion of GRK-2 protein by stable transfection of full-length antisense OK-GRK2 cDNA blocked the desensitization of alpha2C-adrenergic receptors but not of 5-HT1B receptors [20].

Other interactions of Adrbk1

• In conclusion, myocardial mRNA and protein levels of GRK2, GRK5, and beta-arrestin-1 are induced in postinfarction failure in rats [1].
• Coexpression of GRK2 and beta-arrestin-2 suppressed GnRH-induced IP3 production more than that of either alone [21].
• We also found that the mRNA ratio of B2AR and BARK1 was well correlated with the preservation of the LVPDP [22].
• Adeno-GRK2-infected cells showed a GRK2 immunoreactivity of about 2.5 (OD405) and LH secretion of 2.5 ng/ml [13].
• GRK2 is a member of the G protein-coupled receptor kinase family that phosphorylates the activated form of beta-adrenergic and other G protein-coupled receptors and plays an important role in their desensitization and modulation [3].

Analytical, diagnostic and therapeutic context of Adrbk1

• Seventy-two hours later, GRK2 expression was measured by enzyme-linked immunosorbent assay, and GnRH-stimulated LH secretion (10(-7) M GnRH-A for 90 min) was assayed by RIA [13].
• Immunohistocytochemistry and confocal microscopy confirmed that GRK-2 and caveolin-1 colocalize in VSM [16].
• Northern blot analysis revealed the presence of GRK2 mRNA transcripts of 5.0 and 3.0 kb in OK cells [20].
• Moreover, S100A1 gene therapy preserved the cardiac beta-adrenergic inotropic reserve, which was associated with the attenuation of GRK2 up-regulation [23].
• To identify the GRK involved, we set up in this study a primary cell culture retaining the morphological and functional characteristics of myometrial tissue as well as the in vivo pattern of GRK expression (GRK2, GRK5, and GRK6) [24].

References