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10.1111/bph.13522 http://scihub22266oqcxt.onion/10.1111/bph.13522 C5406383!5406383!27243554     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Br+J+Pharmacol 2017 ; 174 (10): 1077-89 Nephropedia Template TP {{tp|p=27243554|t=2017. Signal transduction pathways activated by insulin?like peptide 5 at the relaxin family peptide RXFP4 receptor |pdf=|usr=}}{{27243554}} gab.com Text Signal transduction pathways activated by insulin like peptide 5 at the relaxin family peptide RXFP4 receptor JO: Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=27243554 #FOAvip Background and Purpose: Insulin?like peptide 5 (INSL5) is a two?chain, three?disulfide?bonded peptide of the insulin/relaxin superfamily, uniquely expressed in enteroendocrine l?cells of the colon. It is the cognate ligand of relaxin family peptide RXFP4 receptor that is mainly expressed in the colorectum and enteric nervous system. This study identifies new signalling pathways activated by INSL5 acting on RXFP4 receptors. Experimental Approach: INSL5/RXFP4 receptor signalling was investigated using AlphaScreen® proximity assays. Recruitment of G?i/o proteins by RXFP4 receptors was determined by rescue of Pertussis toxin (PTX)?inhibited cAMP and ERK1/2 responses following transient transfection of PTX?insensitive G?i/o C351I mutants. Cell proliferation was studied with bromodeoxyuridine. RXFP4 receptor interactions with ??arrestins, GPCR kinase 2 (GRK2), KRas and Rab5a was assessed with real?time BRET. Gene expression was investigated using real?time quantitative PCR. Insulin release was measured using HTRF and intracellular Ca2+ flux monitored in a Flexstation® using Fluo?4?AM. Key Results: INSL5 inhibited forskolin?stimulated cAMP accumulation and increased phosphorylation of ERK1/2, p38MAPK, Akt Ser473, Akt Thr308 and S6 ribosomal protein. cAMP and ERK1/2 responses were abolished by PTX and rescued by mG?oA, mG?oB and mG?i2 and to a lesser extent mG?i1 and mG?i3. RXFP4 receptors interacted with GRK2 and ??arrestins, moved towards Rab5a and away from KRas, indicating internalisation following receptor activation. INSL5 inhibited glucose?stimulated insulin secretion and Ca2+ mobilisation in MIN6 insulinoma cells and forskolin?stimulated cAMP accumulation in NCI?H716 enteroendocrine cells. Conclusions and Implications: Knowledge of signalling pathways activated by INSL5 at RXFP4 receptors is essential for understanding the biological roles of this novel gut hormone. Linked Articles: This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc Twit Text FOAVip Signal transduction pathways activated by insulin like peptide 5 at the relaxin family peptide RXFP4 receptor ????Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=27243554 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27243554 #FOAvip English Wikipedia <ref>{{Cite pmid|27243554}}</ref> Signal transduction pathways activated by insulin?like peptide 5 at the relaxin family peptide RXFP4 receptor #MMPMID27243554 Ang SY; Hutchinson DS; Patil N; Evans BA; Bathgate RAD; Halls ML; Hossain MA; Summers RJ; Kocan M Br J Pharmacol 2017[May]; 174 (10): 1077-89 PMID27243554show ga Background and Purpose: Insulin?like peptide 5 (INSL5) is a two?chain, three?disulfide?bonded peptide of the insulin/relaxin superfamily, uniquely expressed in enteroendocrine l?cells of the colon. It is the cognate ligand of relaxin family peptide RXFP4 receptor that is mainly expressed in the colorectum and enteric nervous system. This study identifies new signalling pathways activated by INSL5 acting on RXFP4 receptors. Experimental Approach: INSL5/RXFP4 receptor signalling was investigated using AlphaScreen® proximity assays. Recruitment of G?i/o proteins by RXFP4 receptors was determined by rescue of Pertussis toxin (PTX)?inhibited cAMP and ERK1/2 responses following transient transfection of PTX?insensitive G?i/o C351I mutants. Cell proliferation was studied with bromodeoxyuridine. RXFP4 receptor interactions with ??arrestins, GPCR kinase 2 (GRK2), KRas and Rab5a was assessed with real?time BRET. Gene expression was investigated using real?time quantitative PCR. Insulin release was measured using HTRF and intracellular Ca2+ flux monitored in a Flexstation® using Fluo?4?AM. Key Results: INSL5 inhibited forskolin?stimulated cAMP accumulation and increased phosphorylation of ERK1/2, p38MAPK, Akt Ser473, Akt Thr308 and S6 ribosomal protein. cAMP and ERK1/2 responses were abolished by PTX and rescued by mG?oA, mG?oB and mG?i2 and to a lesser extent mG?i1 and mG?i3. RXFP4 receptors interacted with GRK2 and ??arrestins, moved towards Rab5a and away from KRas, indicating internalisation following receptor activation. INSL5 inhibited glucose?stimulated insulin secretion and Ca2+ mobilisation in MIN6 insulinoma cells and forskolin?stimulated cAMP accumulation in NCI?H716 enteroendocrine cells. Conclusions and Implications: Knowledge of signalling pathways activated by INSL5 at RXFP4 receptors is essential for understanding the biological roles of this novel gut hormone. Linked Articles: This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc äSignal transduction pathways activated by insulin?like peptide 5 at th(epmc).pdf DeepDyve Pubget Overpricing