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GRK4 gene variants in humans (GRK4 A>65L, A>142V, and A>486V) are associated with Hypertension in several but not all ethnic groups. GRK4 gene variants impair the function of D1R and D3R and abet the function of AT1R. These lead to enhancement of renal sodium reabsorption and impaired ability to excrete a sodium load that eventually leads to hypertension. Acknowledgments
On normal salt diet, renal CuZnSOD and ECSOD proteins were similar but renal MnSOD was lower in hGRK4g486V than Non-T mice and remained low on high salt diet. hGRK4gammawild-type mice were normotensive and hGRK4g142V mice were hypertensive but both were salt-resistant and in normal redox balance. Chronic tempol treatment partially prevented the salt-sensitivity of hGRK4g486V mice.
A novel function of GRK4 on triggering a p53-independent cellular senescence, which involves an intricate signaling network.
the association between GRK4(142V) and a larger decrease in blood pressure with angiotensin receptor blockers in hypertensive patients.
Subgroup analysis for ethnicity showed that rs1024323 locus of GRK4 gene was associated with hypertension in Caucasians (OR =1.826, 95% CI =1.215-2.745, P=0.004) but not in East Asians and Africans. [meta-analysis]
Thus, we provided new insight into the function of GRKs in agonist-unstimulated GPCR trafficking using a recombinant AM1 receptor and further determined the region of the CLR C-tail responsible for this GRK function.
hGRK4gamma(142V) phosphorylates histone deacetylase type 1 and promotes its nuclear export to the cytoplasm, resulting in increased AT1R expression and greater pressor response to angiotensin II.
A high sodium intake markedly increased the obesity risk in variants of GRK4 A486V regardless of sex amongst Korean children.
The C-terminal region of FMRP interacts with a domain of GRK4 mRNA that is folded in four stem loops.
GRK4alpha is more similar to GRK2 than GRK6. A fully ordered kinase C-tail reveals interactions linking the C-tail with important determinants of kinase activity, including the alphaB helix, alphaD helix, and the P-loop
GRK4 genetic polymorphism plays an important role in the regulation of hypertension.
Mutations in GRK4 gene is associated with stress fracture.
Buffalo colostrum beta-lactoglobulin inhibits VEGF-induced angiogenesis by interacting with G protein-coupled receptor kinase
This study provides a mechanism by which GRK4, via regulation of arterial AT(1)R expression and function, participates in the pathogenesis of conduit vessel abnormalities in hypertension.
internalization of agonist-activated D1R is regulated by both SNX5 and GRK4, and that SNX5 is critical to the recycling of the receptor to the plasma membrane
The significant association was also found for rs2960306 polymorphism in the GRK4 gene among Europeans.
GRK-4 polymorphisms predict blood pressure response to dietary modification in Black subjects with mild-to-moderate hypertension.
Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood pressure regulation.
The G-protein-coupled receptor kinase 4 (T-rs1024323-C and T-rs1801058-C) polymorphisms were not associated with a risk of preeclampsia in Northern Han Chinese.
critical role of GRK4, relative to GRK2, in the homologous desensitization of D1 receptors in renal proximal tubule cells.
GRK4gamma gene variants (A>65L, A>142V, and A>486V) in mice causes Hypertension, although Salt Sensitivity depends on which is GRK4gamma variant is present.
The role of GRK2 in chronic ET-1-induced insulin resistance was investigated.
GRK2 inhibits WNT signaling in osteoblasts
Data (including data from transgenic flies) suggest that SNF1A is involved in neuroprotection in this species; AMPK activation in glia (but not neurons) reduces severity of ionic disruption and prolongs recovery of electrical activity in brains of flies in starvation-induced anoxia.
AMPK can function outside of its canonical nutrient-sensing role in specific developmental contexts.
The significance of these findings is that AMPK is important in the regulation of glucagon signaling, suggesting that the organization of metabolic networks is highly conserved and that AMPK plays a prominent role in these networks.
Loss of AMPK activity exacerbates neuronal loss and associated phenotypes in parkin and LRRK transgenic flies.
Data suggest that that an Sgt1/Hsp90-LKB1-AMPK pathway acts redundantly with a microtubule-induced polarity pathway to generate neuroblast cortical polarity, and the absence of neuroblast cortical polarity can produce neuroblast tumors.
AMPK gamma and alpha mutants altered lipid metabolism and showed persistent starvation behaviors.
AMPK supports growth in Drosophila by regulating muscle activity and nutrient uptake in the gut
These results raise the possibility that muscle is one of major tissues in which AMPK plays a critical role on longevity and stress resistance.
activated by AMP in cell-free assays and by stresses that deplete ATP; the phosphorylated DmAMPK alpha subunit was mainly detected in the nucleus
results demonstrate that AMPK has highly conserved roles across metazoan species not only in the control of metabolism, but also in the regulation of cellular structures
LKB1 and AMPK have roles in cell polarity and division [review]
This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating its deactivation. This gene has been linked to both genetic and acquired hypertension.
, G protein-coupled receptor kinase 2, groucho gene related
, g protein-coupled receptor kinase GRK4
, 5'monophosphate-activated kinase
, AMP-activated kinase
, AMP-activated protein kinase
, AMP-dependent kinase
, G protein-coupled receptor kinase 4
, SNF/AMP-activated protein S/T kinase gamma subunit
, adenosine monophosphate-activated protein kinase
, G-protein-coupled receptor kinase 2-like