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10.1074/jbc.M116.726620 http://scihub22266oqcxt.onion/10.1074/jbc.M116.726620 C4946928!4946928 !27226600     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27226600 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Biol+Chem 2016 ; 291 (29 ): 15119-30 Nephropedia Template TP {{tp|p=27226600 |t=2016. Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors |pdf=|usr=}}{{27226600 }} gab.com Text Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=27226600 #FOAvip G protein-coupled receptors (GPCRs) from the secretin-like (class B) family are key players in hormonal homeostasis and are important drug targets for the treatment of metabolic disorders and neuronal diseases. They consist of a large N-terminal extracellular domain (ECD) and a transmembrane domain (TMD) with the GPCR signature of seven transmembrane helices. Class B GPCRs are activated by peptide hormones with their C termini bound to the receptor ECD and their N termini bound to the TMD. It is thought that the ECD functions as an affinity trap to bind and localize the hormone to the receptor. This in turn would allow the hormone N terminus to insert into the TMD and induce conformational changes of the TMD to activate downstream signaling. In contrast to this prevailing model, we demonstrate that human class B GPCRs vary widely in their requirement of the ECD for activation. In one group, represented by corticotrophin-releasing factor receptor 1 (CRF1R), parathyroid hormone receptor (PTH1R), and pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1R), the ECD requirement for high affinity hormone binding can be bypassed by induced proximity and mass action effects, whereas in the other group, represented by glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), the ECD is required for signaling even when the hormone is covalently linked to the TMD. Furthermore, the activation of GLP-1R by small molecules that interact with the intracellular side of the receptor is dependent on the presence of its ECD, suggesting a direct role of the ECD in GLP-1R activation. Twit Text FOAVip Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=27226600 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27226600 #FOAvip English Wikipedia <ref>{{Cite pmid|27226600 }}</ref> Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors #MMPMID27226600 Zhao LH ; Yin Y ; Yang D ; Liu B ; Hou L ; Wang X ; Pal K ; Jiang Y ; Feng Y ; Cai X ; Dai A ; Liu M ; Wang MW ; Melcher K ; Xu HE J Biol Chem 2016[Jul]; 291 (29 ): 15119-30 PMID27226600 show ga G protein-coupled receptors (GPCRs) from the secretin-like (class B) family are key players in hormonal homeostasis and are important drug targets for the treatment of metabolic disorders and neuronal diseases. They consist of a large N-terminal extracellular domain (ECD) and a transmembrane domain (TMD) with the GPCR signature of seven transmembrane helices. Class B GPCRs are activated by peptide hormones with their C termini bound to the receptor ECD and their N termini bound to the TMD. It is thought that the ECD functions as an affinity trap to bind and localize the hormone to the receptor. This in turn would allow the hormone N terminus to insert into the TMD and induce conformational changes of the TMD to activate downstream signaling. In contrast to this prevailing model, we demonstrate that human class B GPCRs vary widely in their requirement of the ECD for activation. In one group, represented by corticotrophin-releasing factor receptor 1 (CRF1R), parathyroid hormone receptor (PTH1R), and pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1R), the ECD requirement for high affinity hormone binding can be bypassed by induced proximity and mass action effects, whereas in the other group, represented by glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), the ECD is required for signaling even when the hormone is covalently linked to the TMD. Furthermore, the activation of GLP-1R by small molecules that interact with the intracellular side of the receptor is dependent on the presence of its ECD, suggesting a direct role of the ECD in GLP-1R activation. |Amino Acid Sequence [MESH] |Amino Acid Substitution [MESH] |Glucagon-Like Peptide 1/metabolism [MESH] |Glucagon-Like Peptide-1 Receptor/*chemistry/genetics/*metabolism [MESH] |Glucagon/metabolism [MESH] |HEK293 Cells [MESH] |Humans [MESH] |Models, Molecular [MESH] |Mutagenesis, Site-Directed [MESH] |Protein Domains [MESH] |Receptors, G-Protein-Coupled/*chemistry/classification/*metabolism [MESH] |Receptors, Glucagon/*chemistry/genetics/*metabolism [MESH] |Recombinant Fusion Proteins/chemistry/genetics/metabolism [MESH] |Sequence Homology, Amino Acid [MESH]Differential Requirement of the Extracellular Domain in Activation of (epmc).pdf DeepDyve Pubget Overpricing