Abstract：
:The molecular mechanisms regulating the trafficking of the CRTH2 receptor are poorly understood. In the present study, we characterize C-terminal tail determinants involved in the agonist-induced trafficking of the CRTH2 receptor for prostaglandin D(2). Our results showed that progressive deletion of C-terminal tail residues from amino acid 395 up to 337 gradually impaired CRTH2 internalization by approximately 50% as measured by ELISA in HEK293 cells. Surprisingly, further deletion of the C-tail to amino acid 328 or 317 resulted in receptor mutants displaying internalization similar to the wild-type receptor. Individual mutations of Asp(330), Ser(331), Glu(332), and Leu(333) to Ala in the C-tail of the full length receptor resulted in a 45% increase in internalization of the receptor mutants relative to the wild-type receptor. Pretreatment with the recycling inhibitor monensin increased internalization of the wild-type receptor but did not affect that of the D330A, S331A, E332A and L333A mutants, indicating that these residues are part of a recycling motif. Further experiments revealed that Asp(330), Ser(331) and Glu(332) are not only involved in receptor recycling, but are also required for promotion of CRTH2 internalization by GRK2 and GRK5. Site-directed mutagenesis identified Thr(347) as a major site for PKC-induced internalization of the receptor. Confocal microscopy revealed that arrestin-3 dissociated from the receptor after agonist stimulation and internalization, suggesting that CRTH2 is a class A G protein-coupled receptor. Our study identified specific amino acids in the CRTH2 receptor C-tail implicated in the agonist-induced internalization and the recycling of the receptor.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Roy SJ,Parent A,Gallant MA,de Brum-Fernandes AJ,Stanková J,Parent JLdoi
10.1016/j.ejphar.2009.12.022subject
Has Abstractpub_date
2010-03-25 00:00:00pages
10-8issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(09)01143-1journal_volume
630pub_type
杂志文章abstract：:Cell-cell interaction through binding of intercellular adhesion molecule (ICAM), B7.1, B7.2 and CD40 on monocytes to their ligands on T-cells plays a number of roles in cytokine . High mobility group box 1 (HMGB1), an abundant and conserved nuclproduction and lymphocyte proliferationear protein, acts in the extracellu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.11.058
更新日期：2013-02-15 00:00:00
abstract：:The effect of intracutaneous adrenaline and noradrenaline (5 X 10(-12) and 5 X 10(-11) mol) was examined on the oedema (Evans blue dye leakage) response of rats to several inflammatory agents. The catecholamines reduced the oedema response to all agents tested except prostaglandin E1 (PGE1) which was significantly pot...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90500-4
更新日期：1979-08-15 00:00:00
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journal_title：European journal of pharmacology
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doi：10.1016/j.ejphar.2006.11.052
更新日期：2007-03-08 00:00:00
abstract：:Pharmacological experiments have implicated a role for serotonin (5-HT)(1A) receptors in the modulation of anxiety. More recent is the interest in corticotropin-releasing hormone (CRH) system as a potential target for the treatment of anxiety disorders. However, selective pharmacological tools for the CRH system are l...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
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更新日期：2003-02-28 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1983-04-22 00:00:00
abstract：:Clinical evidence indicates an antiarrhythmic effect of sulfonylureas, which might be blunted by their vascular action. We wanted to investigate the effect of glibenclamide and the new sulfonylthiourea compound 1-[[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]-sulfonyl]-3 -me thylthiourea (HMR1883) on cardiac ele...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00322-8
更新日期：2000-06-16 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90675-t
更新日期：1992-01-14 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90368-x
更新日期：1981-04-09 00:00:00
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.02.022
更新日期：2009-04-01 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90011-1
更新日期：1985-11-19 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1992-01-07 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1998-08-07 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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更新日期：2008-07-28 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1990-05-03 00:00:00
abstract：:Gamma globin induction remains a promising pharmacological therapeutic treatment mode for sickle cell anemia and beta thalassemia, however Hydroxyurea remains the only FDA approved drug which works via this mechanism. In this regard, we assayed the γ-globin inducing capacity of Cis-vaccenic acid (CVA). CVA induced dif...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：2016-04-05 00:00:00
