Recombinant Human G protein-coupled receptor kinase 4 (GRK4)

1. 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 PMID: 27045027
2. 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. PMID: 28189851
3. A novel function of GRK4 on triggering a p53-independent cellular senescence, which involves an intricate signaling network. PMID: 28912086
4. the association between GRK4(142V) and a larger decrease in blood pressure with angiotensin receptor blockers in hypertensive patients. PMID: 25732908
5. 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] PMID: 26730182
6. 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. PMID: 26820533
7. 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. PMID: 26667412
8. A high sodium intake markedly increased the obesity risk in variants of GRK4 A486V regardless of sex amongst Korean children. PMID: 25768006
9. The C-terminal region of FMRP interacts with a domain of GRK4 mRNA that is folded in four stem loops. PMID: 26250109
10. 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 PMID: 26134571
11. GRK4 genetic polymorphism plays an important role in the regulation of hypertension. PMID: 25870190
12. Mutations in GRK4 gene is associated with stress fracture. PMID: 25023003
13. Buffalo colostrum beta-lactoglobulin inhibits VEGF-induced angiogenesis by interacting with G protein-coupled receptor kinase PMID: 23839509
14. 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. PMID: 24218433
15. 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 PMID: 23195037
16. The significant association was also found for rs2960306 polymorphism in the GRK4 gene among Europeans. PMID: 22639547
17. GRK-4 polymorphisms predict blood pressure response to dietary modification in Black subjects with mild-to-moderate hypertension. PMID: 21544086
18. Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood pressure regulation. PMID: 20153824
19. 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. PMID: 20448640
20. critical role of GRK4, relative to GRK2, in the homologous desensitization of D1 receptors in renal proximal tubule cells. PMID: 12164861
21. role in phosphorylation-independent desensitization of GABA(B) receptor PMID: 12881416
22. Genetic variation in GRK4gamma was associated with hypertension PMID: 15097232
23. GRK4 constitutively phosphorylates the D1 receptor in the absence of agonist activation. PMID: 16338988
24. data indicate that the R65L polymorphism of the GRK4 gene plays a role in blood pressure regulation in adolescents and young adults. PMID: 16461192
25. The 65L allele of GRK4 gene is associated with stress-induced urinary sodium excretion. PMID: 16940246
26. Genetic variation in Gprotein-coupled receptor kinase 4 was associated with hypertension in northern Han Chinese. PMID: 17044852
27. We conclude that the elevated blood pressure of hGRK4gamma A142V transgenic mice is due mainly to the effect of hGRK4gamma A142V transgene acting via D(1)R and increased ROS production is not a contributor. PMID: 17259440
28. This evidence suggests the kinase domain of GRK4gamma is responsible for GPCR regulation and GRK4 binding to inactive Galpha(s) and Gbeta may explain the constitutive activity of GRK4gamma towards Galpha(s)-coupled receptors. PMID: 18190783
29. The GRK4 Ala142Val polymorphism did not contribute to the phenotypes in renal handling of sodium PMID: 18413491
30. The potential implication of GRK4 promoter variation in blood pressure control in humans is unmistakable. PMID: 18711006
31. The 4 identified genetic variants within this region exert allele-specific impact on both cell type- and stimulation-dependent transcription and may affect the expression balance of renal G protein-coupled receptor kinase 4. PMID: 18711008
32. hypertensive African American men with a GRK4 A142 variant were less responsive to metoprolol if they had a GRK4 L65 variant PMID: 19119263
33. GRK4, specifically the GRK4-gamma and GRK4-alpha isoforms, phosphorylates the D(3) receptor and is crucial for its signaling in human proximal tubule cells PMID: 19520868

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HGNC: 4543

OMIM: 137026

KEGG: hsa:2868

STRING: 9606.ENSP00000381129

UniGene: Hs.32959