Ask about this productRelated genes to: GRK4 antibody
- Gene:
- GRK4 NIH gene
- Name:
- G protein-coupled receptor kinase 4
- Previous symbol:
- GPRK2L
- Synonyms:
- GPRK4
- Chromosome:
- 4p16.3
- Locus Type:
- gene with protein product
- Date approved:
- 1993-10-14
- Date modifiied:
- 2015-09-07
Related products to: GRK4 antibody
Related articles to: GRK4 antibody
- G protein‑coupled receptor kinase 4 (GRK4) is a member of the receptor phosphorylating GRK family with a well characterized function in renal sodium reabsorption through the modulation of dopaminergic receptors in adults. During embryonic development, GRK4 controls renal cilium development and thus, kidney function. The loss of GRK4 in zebrafish embryos results in pronephric dilatation, massive cilium elongation, glomerular cyst formation and, as a consequence of renal dysfunction, brain edema such as hydrocephalus. Notably, these embryonic functions of GRK4 appear to be independent of G protein‑coupled receptor modulation, although the full extent of the abilities of GRK4 to modulate cellular signaling has remained unclear. The present study aimed to provide further insight on this aspect of the functions of GRK4. Using zebrafish embryos, the present study demonstrates that GRK4 is required for normal pronephros patterning. The loss of Grk4 resulted in the upregulation of the sodium‑hydrogen exchanger 3a (Nhe3a), the zebrafish homologue of human NHE3. The administration of the NHE3 inhibitor, tenapanor, restored normal kidney development and function. Of note, during embryogenesis, this modulation of Nhe3a is not connected to dopaminergic receptor signaling or to a possible nuclear function of GRK4. Instead, the present study identified elevated Stat3 activity as the underlying cause leading to increased Nhe3a transcription and subsequently, to defects in kidney development. - Source: PubMed
Publication date: 2026/08/14
Vu Linh Anna TrúcGerhards JulianMaerz Lars DBurkhalter Martin DPhilipp Melanie - Hypertension continues to be a major global public health challenge. Dopamine generated in the kidney is a vital coordinator of sodium homeostasis and blood pressure control. Dopamine exerts its effects by activating its receptors, which are divided into the D-like receptor family (DR and DR) and the D-like receptor family (DR, DR, and DR). All five dopamine receptor subtypes are differentially expressed along the nephron. Dopamine receptors inhibit the activities and/or expression of renal tubular sodium transporters/exchangers/channels, decrease renal oxidative stress, and interact with other receptors, including angiotensin II receptors. Many studies have demonstrated that renal dopamine receptors play an important role in the regulation of blood pressure. The germline deletion or renal-selective silencing of any of the five dopamine receptor subtypes may impair sodium excretion and increase blood pressure. In addition, renal dopamine receptor expression and/or function are regulated by some factors such as G protein-coupled receptor kinases, oxidative stress, and sorting nexins. In this article, we summarize the role of each dopamine receptor subtype in the pathogenesis of hypertension and discuss the potential regulatory mechanisms of their expression and function. These may lead to the development of novel therapeutic approaches to the prevention and treatment of hypertension. - Source: PubMed
Publication date: 2026/04/02
Yang JianJose Pedro A - - Source: PubMed
Publication date: 2026/04/21
Hua RuifangSu ZhaohaiLin XiangZeng GuozhongYang JiangyongWu TianzhuHe WenxiuJiang FuchengHuang WeihanWang MengyaoWang JichongLin DuFeng YunPei Fang - High-altitude hypoxia is a well-established risk factor for acute kidney injury (AKI), yet effective therapeutic options remain scarce. Salidroside, the primary active compound extracted from Rhodiola, has been reported to protect against hypoxia-induced damage in various organs. Here, we aimed to determine whether salidroside could alleviate kidney injury caused by acute high-altitude exposure and to investigate its underlying mechanisms. To this end, male Sprague-Dawley rats were exposed to hypobaric hypoxia simulating an altitude of 5000 meters and were treated with different doses of salidroside. Kidney injury biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin C (Cys-C), were measured in serum and urine. Histological analysis and protein expression levels of dopamine D1-like receptor (DRD1) and G protein-coupled receptor kinase 4 (GRK4) were also evaluated. In parallel, primary renal proximal tubular (RPT) cells from rats were cultured under hypoxic conditions to validate the findings in vitro, with additional groups receiving DRD1-targeting siRNA or the DRD1 agonist fenoldopam. Salidroside significantly reduced biomarker levels of kidney injury in vivo, preserved DRD1 expression, and inhibited GRK4 upregulation in a time- and dose-dependent manner. Likewise, in vitro treatment with salidroside enhanced cell viability and decreased apoptosis while restoring DRD1 levels and downregulating GRK4. Notably, the protective effects were abolished by DRD1 knockdown and enhanced by fenoldopam, indicating a DRD1-dependent mechanism. Molecular docking analysis further supported these results by demonstrating strong binding affinities between salidroside and both DRD1 and GRK4. Together, our findings suggest that salidroside attenuates hypoxia-induced renal injury through modulation of intrarenal dopamine signaling and highlight its potential as a preventive or therapeutic agent for individuals exposed to hypobaric hypoxia. - Source: PubMed
Publication date: 2026/03/31
Huan ChengZhilin GanDan XiaoYue WangXianglian LiLiwen MoYue Cheng - G protein-coupled receptor kinase 4 (GRK4) plays a vital role in the regulation of blood pressure. Several GRK4 gene variants have attracted attention because of their association with hypertension. However, the role of GRK4 R65L in hypertension is still unclear. In the present study, we report that global and renal tubule-targeted GRK4 R65L over-expression in mice caused salt-sensitive hypertension, accompanied by a rightward shift of the plot of urine sodium excretion against systolic blood pressure, that were improved by AAV9-mediated renal GRK4 depletion. RNA sequencing showed that the expression of the long chain L-2-hydroxyacid oxidase 2 (Hao2) gene ranked first in up-regulated candidates involved in the regulation of sodium-water metabolism. The salt-sensitive hypertension and increased renal oxidative stress in GRK4 R65L mice were mitigated by AAV9-mediated renal Hao2 depletion or administration of the potent antioxidant tempol. Immunoprecipitation-mass spectrometry showed an increased interaction between triosephosphate isomerase 1 (TPI1) and GRK4 in the kidneys of high salt-fed GRK4 R65L mice, accompanied by increased TPI1 phosphorylation and nuclear translocation, which were decreased, along with renal Hao2 expression, after GRK4 depletion. Renal H3K27ac levels and binding to the Hao2 promoter were increased but the levels of nuclear dihydroxyacetone phosphate (DHAP), a downstream molecule of TPI1, were decreased in high salt-fed GRK4 R65L mice. DHAP reduced the levels of H3K27ac and Hao2 in GRK4 R65L transfected-HK-2 cells. The H3K27ac inhibitor C646 mitigated the salt-sensitive hypertension in GRK4 R65L mice, accompanied by decreased H3K27ac and Hao2 expressions, and oxidative stress. Our results demonstrated that in high salt fed-GRK4 R65L mice, elevated renal TPI1 nuclear phosphorylation decreased DHAP levels and increased H3K27ac expression, which increased Hao2 expression and oxidative stress, caused a rightward shift of the pressure-natriuresis plot, and subsequently caused salt-sensitive hypertension. - Source: PubMed
Publication date: 2025/12/15
Zhang FuweiWan JindongJiang LianghongLin XiaoqianChen LinShao MuqingChen JiayaoWang LuningZheng ShuoRen HongmeiChen CaiyuJose Pedro AZeng ChunyuYang Jian