Cloning and Chromosomal Localization of the Human A2b Adenosine Receptor Gene (ADORA2B) and Its Pseudogene

Jacobson, Marlene A.; Johnson, Robert G.; Luneau, Christopher J.; Salvatore, Christopher

doi:10.1006/geno.1995.1061

Cited by 43 publications

(27 citation statements)

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“…Our data is in agreement with others who, using antibody to another epitope in the A2bR, observed that the A2bR had a similar molecular mass of 42 kDa (32,33) in human lymphocytes and CHO cells transfected with the native receptor. The A2bR is known to have two promoters and in addition, a pseudogene located on chromosome 1 (34). Alternate splicing resulting in protein sequence heterogeneity similar to that observed in several other receptors such as dopamine receptor; EP3 receptor has been proposed for the A2bR (3).…”

Section: Discussionmentioning

confidence: 99%

The Adenosine 2b Receptor Is Recruited to the Plasma Membrane and Associates with E3KARP and Ezrin upon Agonist Stimulation

Sitaraman

Wang

Wong

et al. 2002

Journal of Biological Chemistry

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We have previously shown that adenosine is formed in the intestinal lumen during active inflammation from neutrophil-derived 5-AMP. Acting through the adenosine A2b receptor (A2bR), the luminally derived adenosine induces vectorial chloride secretion and a polarized secretion of interleukin-6 to the intestinal lumen. Although some G protein-coupled receptors interact with anchoring or signaling molecules, not much is known in this critical area for the A2bR. We used the model intestinal epithelial cell line, T84, and Caco2-BBE cells stably transfected with GFP-A2b receptor to study the intestinal A2bR. The A2bR is present in both the apical and basolateral membranes of intestinal epithelia. Apical or basolateral stimulation of the A2bR induces recruitment of the receptor to the plasma membrane and caveolar fractions. The A2bR co-immunoprecipitates with E3KARP and ezrin upon agonist stimulation. Ezrin interacts with E3KARP and PKA and the interaction between ezrin and E3KARP is enhanced by agonist stimulation. Our data suggest that the A2bR is recruited to the plasma membrane upon apical or basolateral agonist stimulation and interacts with E3KARP and ezrin. We speculate that such an interaction may not only anchor the A2bR to the plasma membrane but may also function to stabilize the receptor in a signaling complex in the plasma membrane.

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Section: Discussionmentioning

confidence: 99%

The Adenosine 2b Receptor Is Recruited to the Plasma Membrane and Associates with E3KARP and Ezrin upon Agonist Stimulation

Sitaraman

Wang

Wong

et al. 2002

Journal of Biological Chemistry

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“…The responding human gene was localized to chromosome 17p12 (151). There is only sparse information on the presence of adenosine A 2b adenosine receptors in the kidney (see Table 1).…”

Section: B Adenosine a 2a And A 2b Receptorsmentioning

confidence: 99%

Adenosine and Kidney Function

Vallon

Mühlbauer²,

Oßwald³

2006

Physiological Reviews

401

379

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In this review we outline the unique effects of the autacoid adenosine in the kidney. Adenosine is present in the cytosol of renal cells and in the extracellular space of normoxic kidneys. Extracellular adenosine can derive from cellular adenosine release or extracellular breakdown of ATP, AMP, or cAMP. It is generated at enhanced rates when tubular NaCl reabsorption and thus transport work increase or when hypoxia is induced. Extracellular adenosine acts on adenosine receptor subtypes in the cell membranes to affect vascular and tubular functions. Adenosine lowers glomerular filtration rate (GFR) by constricting afferent arterioles, especially in superficial nephrons, and acts as a mediator of the tubuloglomerular feedback, i.e., a mechanism that coordinates GFR and tubular transport. In contrast, it leads to vasodilation in deep cortex and medulla. Moreover, adenosine tonically inhibits the renal release of renin and stimulates NaCl transport in the cortical proximal tubule but inhibits it in medullary segments including the medullary thick ascending limb. These differential effects of adenosine are subsequently analyzed in a more integrative way in the context of intrarenal metabolic regulation of kidney function, and potential pathophysiological consequences are outlined.

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“…To date, genes encoding four adenosine receptors have been isolated (Ren and Stiles, 1994b;Jacobson et al, 1995;Chu et al, 1996;Atkinson et al, 1997). A unique and conserved feature in these adenosine receptor subtype genes is the location of an intron in the second intracellular loop of the receptor proteins.…”

Section: Discussionmentioning

confidence: 99%

The 5' Untranslated Regions of the Rat A_2A Adenosine Receptor Gene Function as Negative Translational Regulators

Lee

Chang

et al. 1999

Journal of Neurochemistry

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Abstract:The rat A 2A adenosine receptor (A 2A -R) gene contains two promoters, P1 and P2, which produce transcript 1 and transcript 2, respectively. These transcripts differ in the lengths of their 5Ј untranslated regions (5ЈUTR1: 514 bp, initiated from P1; 5ЈUTR2: 221 bp, initiated from P2) but encode the same protein. In the present study, we demonstrate that transcript 2 is present in various tissues at different levels, whereas transcript 1 is found only in the striatum. In the striatum, the level of transcript 2 is ϳ300-fold higher than that of transcript 1. The 5ЈUTR of both transcripts suppresses the expression of A 2A -R and a firefly luciferase reporter gene at the translational level; this suppression is not observed after mutational inactivation of an "out-offrame" upstream AUG codon. Translational suppression by the 5ЈUTR was also confirmed in cells using a bicistronic strategy. Collectively, these data suggest that P2 is the major promoter of the rat A 2A -R gene. The 5ЈUTR of the rat A 2A -R gene exerts an inhibitory effect on translation by an upstream open reading frame. Because the 5ЈUTR of the A 2A -R gene possesses strong interspecies homology, translational suppression may be a general mechanism by which the expression of the A 2A -R gene is regulated.

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Cloning and Chromosomal Localization of the Human A2b Adenosine Receptor Gene (ADORA2B) and Its Pseudogene

Cited by 43 publications

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The Adenosine 2b Receptor Is Recruited to the Plasma Membrane and Associates with E3KARP and Ezrin upon Agonist Stimulation

The Adenosine 2b Receptor Is Recruited to the Plasma Membrane and Associates with E3KARP and Ezrin upon Agonist Stimulation

Adenosine and Kidney Function

The 5' Untranslated Regions of the Rat A_2A Adenosine Receptor Gene Function as Negative Translational Regulators

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Cloning and Chromosomal Localization of the Human A2b Adenosine Receptor Gene (ADORA2B) and Its Pseudogene

Cited by 43 publications

References 0 publications

The Adenosine 2b Receptor Is Recruited to the Plasma Membrane and Associates with E3KARP and Ezrin upon Agonist Stimulation

The Adenosine 2b Receptor Is Recruited to the Plasma Membrane and Associates with E3KARP and Ezrin upon Agonist Stimulation

Adenosine and Kidney Function

The 5' Untranslated Regions of the Rat A2A Adenosine Receptor Gene Function as Negative Translational Regulators

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The 5' Untranslated Regions of the Rat A_2A Adenosine Receptor Gene Function as Negative Translational Regulators