Recombinant Mouse Beta-adrenergic receptor kinase 1 (Grk2)

1. Enhanced GRK2 expression triggers cardiac hypertrophy by GRK2-PI3Kgamma mediated Akt phosphorylation and subsequent inactivation of GSK3beta. PMID: 28759639
2. Grk2 rescuing activity requires the integrity of domains essential for its interaction with GPCRs, we speculate that Grk2 may regulate Hh pathway activity by downregulation of a GPCR. PMID: 27113758
3. The main novelty presented here is to show that septic shock induces cardiac hyporesponsiveness to isoproterenol by a mechanism dependent on nitric oxide and mediated by G protein-coupled receptor kinase isoform 2. Therefore, G protein-coupled receptor kinase isoform 2 inhibition may be a potential therapeutic target in sepsis-induced cardiac dysfunction. PMID: 28526706
4. Data, including data from studies in heterozygous knockout mice, suggest that Grk2 is involved in TNFalpha-induced wound healing in epithelial cells of the colon; Grk2 appears to inhibit TNFalpha-induced apoptosis; Grk2 inhibits TNFalpha-induced ERK activation by inhibiting generation of reactive oxygen species. Homozygous knockout of Grk2 is embryonically lethal in mice. PMID: 28572156
5. GRK2 upregulation causes kappa-opioid receptor desensitization in diabetic heart PMID: 27865836
6. study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as beta2AR-induced hypertrophy. PMID: 27566547
7. GRK2 loss confers a protective advantage over control mice after myocardial ischemia/reperfusion injury. Fibroblast GRK2 knockout mice presented with decreased infarct size and preserved cardiac function 24 hours post ischemia/reperfusion. They had decreased fibrosis and fibrotic gene expression. These protective effects correlated with decreased infiltration of neutrophils to the ischemia site and decreased TNF-alpha. PMID: 27601479
8. this study shows that astragaloside IV alleviates E. coli-caused peritonitis through modulating GRK2-CXCR2 signal in neutrophils PMID: 27543854
9. GRK2 down-regulation is cardioprotective during diet-induced obesity, reinforcing the protective effect of maintaining low levels of GRK2 under nutritional stress, and showing a role for this kinase in obesity-induced cardiac remodeling and steatosis. PMID: 27832814
10. The betaARKrgs peptide, but not endogenous GRK2, interacted with Galpha(q) and interfered with signaling through this G protein. These data support the development of GRK2-based therapeutic approaches to prevent hypertrophy and heart failure. PMID: 27016525
11. GRK2 is localized in the mitochondria and its kinase activity negatively impacts the function of this organelle by increasing superoxide levels and altering substrate utilization for energy production. PMID: 26506135
12. Erythropoietin seems to reverse sepsis-induced vasoplegia to NE through the preservation of alpha1D adrenoceptor mRNA/protein expression, inhibition of GRK2-mediated desensitization, and attenuation of NO overproduction in the mouse aorta. PMID: 26025460
13. In vitro, GRK2 inhibits Epac1-to-Rap1 signaling by phosphorylation of Epac1 at Ser-108 in the Disheveled/Egl-10/pleckstrin domain. GRK2 inhibits Epac1-mediated sensitization of Piezo2 which contributes to inflammatory mechanical hyperalgesia. PMID: 26929333
14. GRK2 ablation increases circadian amplitude and decreases circadian period. GRK2 suppresses mPeriod1 transcription,PERIOD1/2 nuclear trafficking and promotes PERIOD2 phosphorylation. PMID: 26279567
15. These results suggest GRK2 contributes to melanopsin deactivation, but that other mechanisms account for most of modulation of melanopsin activity in ipRGCs. PMID: 26069965
16. data suggest that inhibiting GRK2 could reverse an established insulin-resistant and obese phenotype PMID: 26198359
17. Post-MI AdipoR1 phosphorylation positively correlated with the expression level of GRK2. AdipoR1 is phosphorylatively modified and desensitized by GRK2 in failing cardiomyocytes, contributing to post-MI remodeling and HF progression. PMID: 25696921
18. findings indicate that the balance between mechanisms regulating vascular tone are shifted to favor vasoconstriction in the absence of GRK2 expression and that this leads to the age-dependent development of hypertension PMID: 25561731
19. Data indicate that G protein-coupled receptor kinase 2 (GRK2) downregulation enhances insulin signaling in adult mouse hearts. PMID: 25239306
20. Findings reveal a cell-type-specific role for GRK2 in the regulation of normal motor behavior, sensitivity to psychostimulants, dopamine neurotransmission, and D2 autoreceptor function PMID: 24776686
21. Attenuation of GRK2 is associated with defective differentiation of somatic muscles. PMID: 24927997
22. These data demonstrate that GRK2 modulates FcinRI signaling in mast cells via at least two mechanisms.One involves GRK2-RH and modulates tyrosine phosphorylation of Syk, and the other is mediated via the phosphorylation of p38 and Akt. PMID: 24904059
23. Data indicate that ischemic injury coupled to G protein-coupled receptor beta1/2 adrenergic receptors activation required GRK2 (GPCR kinase 2) activation. PMID: 24170934
24. Our results describe an important role for GRK2 in systemic hypertension. PMID: 24191280
25. GRK2 blockade with betaARKct is essential for cardiac beta2-adrenergic receptor signaling towards increased contractility. PMID: 23984976
26. decreased endothelial Grk2 dosage accelerated tumor growth, along with reduced pericyte vessel coverage and enhanced macrophage infiltration, and this transformed environment promoted decreased GRK2 in endothelial cells PMID: 24135140
27. GRK2 removal compromises vascular phenotype and integrity by increasing endothelial reactive oxygen species production. PMID: 23950144
28. These findings underline the critical role of GRK2 regulation in astrocytes for dampening the extent of brain damage after ischemia. PMID: 23313319
29. TNFalpha-induced betaAR desensitization is mediated by GRK2 and is independent of Gbetagamma, uncovering a hitherto unknown cross-talk between TNFalpha and betaAR function, providing the underpinnings of inflammation-mediated cardiac dysfunction. PMID: 23785004
30. study identified a novel interaction between TLR4 and chemokine receptors that can control monocyte migration, an essential component of innate immune response; results support a model in which LPS-TLR4 signaling augments monocyte migration by modulating cell surface expression of chemokine receptors in a GRK2-dependent manner PMID: 23772028
31. GRK2 plays a key role in modulating the aortic vasodilator effect of clonidine by selectively affecting the Akt/eNOS pathway, especially in males. PMID: 22925038
32. GRK2 localizes to mitochondria, providing novel insight into GRK2-dependent pathophysiological signaling mechanisms in wild-type mice. PMID: 23467820
33. Inhibition of G-protein-coupled receptor kinase 2 (GRK2) triggers the growth-promoting mitogen-activated protein kinase (MAPK) pathway PMID: 23362259
34. even partial hematopoietic GRK2 deficiency prevents atherosclerotic lesion progression beyond the fatty streak stage, identifying hematopoietic GRK2 as a potential target for intervention in atherosclerosis PMID: 23047899
35. GRK2 knockdown increases chemokine CXCR1-mediated exocytosis but decreases receptor phosphorylation and internalization. PMID: 22869904
36. This study demonstrated that the elimination of GRK2 in cholinergic neurons reduces sensitivity to select muscarinic-mediated behaviors PMID: 22895728
37. hemizygous mice displayed better thermogenic capacity and exhibited more oxidative phenotype in both BAT and WAT than WT littermates. Overexpression of GRK2 in brown adipocytes corroborated the negative effect in BAT function and differentiation PMID: 22516294
38. G protein-coupled receptor kinase 2 inhibitor normalizes vascular endothelial function in type 2 diabetic mice by improving beta-arrestin 2 translocation and ameliorating Akt/eNOS signal dysfunction PMID: 22581458
39. After beta-adrenergic stimulation, GRK2KO myocytes increased in contractility & Ca(2+) transients, not mediated through cardiac L-type Ca(2+) channels but thru increased SR Ca(2+), a novel form of differential regulation. PMID: 22496128
40. The data show a novel sub-cellular localization of GRK2 in the mitochondria and an unexpected role in regulating mitochondrial biogenesis and ATP generation. PMID: 21983013
41. Angiotensin II causes endothelial dysfunction in diabetes via the Akt/eNOS pathway, and an increase in plasma Angiotensin II increases the vascular GRK2 level. PMID: 21571071
42. Mouse models of chronic pain are associated with reduced cellular levels of GRK2. GRK2 is a newly discovered major player in the regulation of chronic pain. Review. PMID: 21473908
43. GRK2 functions in downregulation of S1PR1 on blood-exposed lymphocytes; GRK2-dependent S1PR1 desensitization allows lymphocytes to escape circulatory fluids and migrate to lymphoid tissues PMID: 21960637
44. Report dysfunctional endothelium-dependent relaxation to insulin via PKC-mediated GRK2/Akt activation in aortas of type 2 diabetic mice. PMID: 21572010
45. GRK2 is pathological in the injured heart;it is a critical mechanistic link within neurohormonal crosstalk governing cardiac contractile signaling/function through beta-adrenergic receptors and metabolism through the insulin receptor PMID: 21518983
46. role in chondrocyte mechanotransduction PMID: 21520257
47. These studies reveal previously undescribed negative regulatory role for GRK2 in TLR4-induced p105-ERK pathway as well as in the consequent inflammatory cytokine/chemokine production and endotoxemia in mice. PMID: 20717897
48. The evidence provided points toward the possibility that the acceleration of GIRK current desensitization by GRK2 is due to competition for Gbetagamma dimers with the channel. PMID: 21111235
49. desensitization of the dopamine D1-D2 receptor heteromer-mediated signal can occur by agonist occupancy even without activation and is dually regulated by both the catalytic and RGS domains of GRK2. PMID: 20807772
50. In vivo, low nociceptor GRK2 leads to prolonged inflammatory hyperalgesia via biased cAMP signaling from PKA to Epac-Rap1, ERK/PKCepsilon pathways. PMID: 20861385

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KEGG: mmu:110355

STRING: 10090.ENSMUSP00000025791

UniGene: Mm.254144