کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815760 | 1058502 | 2011 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Role of Ãarrestins in bradykinin B2 receptor-mediated signalling
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کلمات کلیدی
Bradykinin type 2 receptorPTH1RV2RGPCRsG protein receptor kinaseB2RGRKPKCmRFPNK-1RAT1RYFPPAR-2ERK1/2 - ERK1 / 2G protein-coupled receptors - G گیرنده های پروتئینی همراهMAPK - MAPKangiotensin II type 1 receptor - آنژیوتانسین II نوع 1 گیرندهbradykinin B2 receptor - برادیکینین B2 گیرندهbradykinin - برادیکینینvasopressin type 2 receptor - واپرسین نوع 2 گیرندهyellow fluorescent protein - پروتئین فلورسنت زردmonomeric red fluorescent protein - پروتئین فلورسنت قرمز مونومرextracellular signal-regulated protein kinases - پروتئین کیناز سلول های تنظیم شده با سیگنالProtein kinase C - پروتئین کیناز سیmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenextracellular signal-regulated kinase 1/2 - کیناز 1/2 تنظیم سیگنال خارج سلولیNeurokinin-1 receptor - گیرنده نوروکینین-1parathyroid hormone receptor - گیرنده هورمون پاراتیروئیدprotease-activated receptor - گیرنده پروتئاز فعالG protein-coupled receptor - گیرندههای جفتشونده با پروتئین جی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
G protein-coupled receptors (GPCRs) can engage multiple pathways to activate ERK1/2 via both G proteins and/or Ãarrestin. Receptor recruitment of Ãarrestin is also important for GPCR desensitization, internalization and resensitization. Modulation of the receptor/Ãarrestin interaction through modification of either component would presumably alter the output generated by receptor activation. Here we examined how Ãarrestins regulate bradykinin (BK) B2 receptor (B2R) signalling and desensitization by either truncating Ãarrestin1 or Ãarrestin2 or by alanine substitution of a serine/threonine cluster in the C-terminal tail of B2R (B2R-4A), conditions which all affect the avidity of the B2R/Ãarrestin complex. We first demonstrate that BK-mediated ERK1/2 activation is biphasic containing an early peak (between 2-5 min) followed by sustained activation for at least 60 min. The early but not the sustained phase was predictably affected by inhibition of either Gαq/11 or Gαi/o, whereas loss of Ãarrestin2 but not Ãarrestin1 resulted in diminished prolonged ERK1/2 activation. Ãarrestin2's role was further examined using a truncation mutant with augmented avidity for the agonist-occupied receptor, revealing an increase in both immediate and extended ERK1/2 signalling. We also show that ERK1/2 is recruited to the B2R/Ãarrestin complex on endosomes as well as the plasma membrane. Moreover, we investigated Ãarrestin's role using the B2R-4A, which is deficient in Ãarrestin binding and does not internalize. We show that ERK1/2 signalling downstream of the receptor is entirely G protein-dependent and receptor-mediated intracellular calcium mobilization studies revealed a lack of desensitization. Functionally, the lack of desensitization resulted in increased cell growth and migration compared to the wild-type receptor, which was sensitive to MEK inhibition. These results highlight Ãarrestin's crucial role in the maintenance of proper B2R signalling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 23, Issue 4, April 2011, Pages 648-659
Journal: Cellular Signalling - Volume 23, Issue 4, April 2011, Pages 648-659
نویسندگان
Brandon Zimmerman, May Simaan, Marie-Yvonne Akoume, Nadia Houri, Stéphanie Chevallier, Philippe Séguéla, Stéphane A. Laporte,