Cellular signalling of cysteinyl leukotriene type 1 receptor variants CysLT₁-G300S and CysLT₁-I206S

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• 作者：Louiza Yaddaden^a ; Steeve Vé ; ronneau^a ; Miles D. Thompson^b ; Marek Rola-Pleszczynski^a ; Jana Stankova^a ; ^{jana.stankova@usherbrooke.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：cysLTs ; cysteinyl-leukotrienes ; CysLT1 ; cysteinyl-leukotriene type 1 receptor ; WT ; wild-type ; LT ; leukotriene ; GPCR ; G-protein-coupled receptor
• 刊名：Prostaglandins, Leukotrienes and Essential Fatty Acids
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：105
• 期：Complete
• 页码：1-8
• 全文大小：1194 K

文摘

Cysteinyl-leukotrienes are pro-inflammatory lipid mediators, involved in allergic asthma, that bind the G-protein-coupled receptors CysLT₁, CysLT₂ and GPR99. A polymorphism in one of these receptors, CysLT₁-G300S was strongly associated with atopy, whereas the CysLT₁-I206S polymorphism was not. In the present work, our aim was to characterize these two variants by studying their cellular signalling. Cell surface expression of mutant receptors in transfected HEK-293 cells was comparable to that of the wild-type receptor. Compared to CysLT₁-WT, production of inositol phosphates as well as IL-8 and IL-13 promoter transactivation in response to either LTD₄ or LTC₄ was significantly increased in CysLT₁-G300S-transfected cells. Moreover, LTD₄-induced phosphorylation of the signalling effector Erk, but not p38, p65 or c-Jun was higher in CysLT₁-G300S-transfected cells. On the other hand, the variant CysLT₁-I206S did not show a significant difference in its signal transduction compared to the wild-type receptor. Taken together, our results indicate that the variant CysLT₁-G300S can induce a greater signal than the CysLT₁-WT receptor, a feature that may be relevant to its association with atopy.