Type 1 angiotensin II receptor-associated protein ARAP1 binds and recycles the receptor to the plasma membrane

Guo, Deng‐Fu; Chénier, Isabelle; Tardif, Valérie; Orlov, Sergei N.; Inagami, Tadashi

doi:10.1016/j.bbrc.2003.09.154

Cited by 61 publications

(54 citation statements)

References 49 publications

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“…Identification of GLP Gene-To identify proteins that interact with the carboxyl-terminal domain of the AT 1A receptor, a yeast two-hybrid screen was performed in a system that included the AT 1A (residues 295-359) fused to the lex A DNA binding domain and a mouse embryo cDNA library (37) fused to the VP16 transactivation domain. One positive clone, A8, which contained 162-amino acid residues of mouse GLP (residues 371-533), was isolated.…”

Section: Resultsmentioning

confidence: 99%

“…Overexpression of ATRAP causes a marked inhibition of the AT 1 receptor-mediated activation of phospholipase C. Further studies also demonstrate that ATRAP overexpression enhances AT 1 receptor internalization and inhibits cell growth in VSMCs (36). On the other hand, ARAP1 is another protein that was found to interact with the carboxyl-terminal domain of the AT 1 receptor (37). Characterization of ARAP1 in HEK-293 cells has revealed that ARAP1 binds and promotes the AT 1 receptor to the plasma membrane, indicating its role in the receptor recycling pathway.…”

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confidence: 92%

“…As for many G-protein-coupled receptors, the carboxyl-terminal domain of the AT 1 receptor presumably interacts with G-protein-coupled receptor kinases and arrestins, causing the functional desensitization of the receptor (31)(32)(33). Two novel proteins, ATRAP and ARAP1, have recently been isolated by us and another using the yeast two-hybrid system (35)(36)(37). ATRAP is a small protein that interacts specifically with the carboxyl-terminal domain of the AT 1 receptor (35).…”

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confidence: 99%

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A Novel Angiotensin II Type 1 Receptor-associated Protein Induces Cellular Hypertrophy in Rat Vascular Smooth Muscle and Renal Proximal Tubular Cells

Guo

Tardif

Ghelima

et al. 2004

Journal of Biological Chemistry

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Angiotensin II stimulates cellular hypertrophy in cultured vascular smooth muscle and renal proximal tubular cells. This effect is believed to be one of earliest morphological changes of heart and renal failure. However, the precise molecular mechanism involved in angiotensin II-induced hypertrophy is poorly understood. In the present study we report the isolation of a novel angiotensin II type 1 receptor-associated protein. Angiotensin II (Ang II) 1 elicits a wide range of physiological responses in a variety of cell types. This octapeptide hormone plays an important role in the regulation of cardiovascular and renal functions via diverse mechanisms (1), which include arteriolar vasoconstriction, stimulation of aldosterone production, and electrolyte homeostasis (2). Although its vasoactive effects were initially considered to be a unique feature for maintaining blood pressure, recent studies have demonstrated that Ang II exerts many other important actions on the cardiovascular and renal systems. For example, Ang II stimulates the growth of diverse cell types, such as vascular smooth muscle cells (VSMC), cardiac myocytes, and proximal tubular cells (3-6), and it increases the expression of enzymes that produce mediators of inflammation (7,8). These observations suggest that Ang II may play an important role in various cardiovascular and renal diseases associated with abnormal cell growth (cellular hypertrophy or cell proliferation) and inflammation, such as hypertension, congestive heart failure, atherosclerosis, postangioplastic restenosis, and renal failure. Clinical trials and animal studies demonstrated that angiotensin-converting enzyme inhibitors and Ang II receptor blockers prevented vascular, left ventricular, and renal proximal tubular cellular hypertrophy (9 -13), supporting the importance of Ang II in the pathogenesis of cardiovascular and renal diseases. In vitro, Ang II has also been shown to stimulate the growth of VSMC and renal proximal tubular cells (hypertrophic effect) as well as cardiac myocytes and fibroblasts (hyperplastic action) (14 -17).

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Section: Resultsmentioning

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confidence: 99%

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A Novel Angiotensin II Type 1 Receptor-associated Protein Induces Cellular Hypertrophy in Rat Vascular Smooth Muscle and Renal Proximal Tubular Cells

Guo

Tardif

Ghelima

et al. 2004

Journal of Biological Chemistry

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“…This protein has been shown to accelerate AT1 recycling back to the plasma membrane. 23 Because AT1 plays versatile physiological roles, the present study focused on defining the pathophysiological role of ARAP1 in the renal proximal tubules on its tissue-specific transgenic expression driven by a proximal tubule-specific promoter KAP. We found that proximal tubular ARAP1 transgenic mice have a significant elevation of BP by 20 to 25 mm Hg, which is salt sensitive and can be normalized by inhibition of the RAS by an ACE inhibitor or AT1 receptor blocker.…”

Section: Discussionmentioning

confidence: 99%

“…AT 1 receptor-associated protein (ARAP1) has been identified to directly interact with AT 1 and promote receptor recycling to the plasma membrane in vitro. 23 The objective of the present study was to investigate the pathophysiological function of ARAP1 gene in the kidneys of transgenic mice. For this purpose, we generated transgenic mice overexpressing rat ARAP1 driven by the renal androgenregulated protein (KAP) promoter in the renal proximal tubules.…”

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Development of Hypertension and Kidney Hypertrophy in Transgenic Mice Overexpressing ARAP1 Gene in the Kidney

et al. 2006

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Abstract-Angiotensin II regulates blood pressure via activation of the type 1 receptor. We previously identified a novel angiotensin II type 1 receptor-associated protein and demonstrated that it promotes receptor recycling to the plasma membrane. To delineate the pathophysiological function of the ARAP1 in the kidneys, we generated transgenic mice that overexpress rat ARAP1 cDNA specifically in proximal tubules and tested the hypothesis that proximal tubule-specific overexpression of ARAP1 causes hypertension. Two lines of male transgenic mice, 650 and 670, displayed kidney-specific transgene expression. Systolic blood pressure was significantly elevated by Ϸ20 to 25 mm Hg in these lines of mice at 20 weeks of age compared with their nontransgenic litter mates. Urine volume, but not water intake, was significantly decreased in both lines compared with nontransgenic controls. The kidney/body weight ratio was significantly increased in both lines compared with their nontransgenic litter mates at 12 and 20 weeks of age. In contrast, no difference was observed in the ratio of brain, spleen, heart, and testis to body weight between male transgenic and nontransgenic animals. Inhibitions of the renin-angiotensin system completely normalized the systolic blood pressure of transgenic mice. Moreover, low salt intake prevented the development of hypertension, whereas high salt intake exacerbated the increase in blood pressure in transgenic mice. Therefore, our data show that proximal tubule-specific overexpression of ARAP1 leads to hypertension, suggesting that renal ARAP1 plays an important role in the regulation of blood pressure and renal function via activation of the intrarenal renin-angiotensin system. Key Words: animals, transgenic Ⅲ gene expression H ypertension is a major risk factor for cardiovascular and renal diseases. Although numerous studies have implicated a role for the renin-angiotensin system (RAS) in the development of hypertension, its mechanisms remain incompletely understood. Traditionally, the hypertensive effects of the RAS were considered to be the actions of circulating components of this system. According to this view, angiotensin II (Ang II) in the systemic circulation is generated from angiotensinogen (AOGEN), which is acted on by renin from the kidneys to proteolytically produce angiotensin I, a substrate being further processed by angiotensin-converting enzyme (ACE) to form biologically active Ang II. However, recent convincing evidence accumulated from physiological, biochemical, and molecular studies has demonstrated other pathways of Ang II production. Among these, the intrarenal RAS is of special interest. Renal proximal tubules contain all of the components of the RAS. [1][2][3] It has been demonstrated that activation of the Ang II type 1 receptor (AT 1 ) stimulates the apical sodium-hydrogen exchanger in proximal tubules 4 and augments epithelial sodium channel (ENaC) activity in the collecting ducts, 5,6 leading to modulation of blood pressure (BP) and fluid homeostasis. Furthermore...

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Regulationsmechanismen des Renin-Angiotensin-Systems im kardiovaskulären System

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Type 1 angiotensin II receptor-associated protein ARAP1 binds and recycles the receptor to the plasma membrane

Cited by 61 publications

References 49 publications

A Novel Angiotensin II Type 1 Receptor-associated Protein Induces Cellular Hypertrophy in Rat Vascular Smooth Muscle and Renal Proximal Tubular Cells

A Novel Angiotensin II Type 1 Receptor-associated Protein Induces Cellular Hypertrophy in Rat Vascular Smooth Muscle and Renal Proximal Tubular Cells

Development of Hypertension and Kidney Hypertrophy in Transgenic Mice Overexpressing ARAP1 Gene in the Kidney

Regulationsmechanismen des Renin-Angiotensin-Systems im kardiovaskulären System

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