Receptor component protein, an endogenous allosteric modulator of family B G protein coupled receptors
| Autor: | Sarah J Routledge, Ho Yan Yeung, David R. Poyner, John Simms, Graham Ladds, Ashley J. Clark, Philip Kitchen, Ian M. Dickerson, Mark Wigglesworth |
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| Přispěvatelé: | Ladds, Graham [0000-0001-7320-9612], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Accessory protein Peptide Hormones AM Adrenomedullin Ligands Biochemistry CGRP calcitonin gene-related peptide Receptor Activity-Modifying Protein 1 Receptors G-Protein-Coupled Adrenomedullin 0302 clinical medicine Cyclic AMP CGRP Calcitonin receptor Receptor TM transmembrane helix GPCR signalling Chemistry RCP receptor component protein GIP gastric inhibitory polypeptide Calcitonin Receptor-Like Protein CT calcitonin CRF corticotrophin releasing factor 3. Good health Cell biology GLP glucagon-like polypeptide hormones hormone substitutes and hormone antagonists Signal Transduction Allosteric modulator Calcitonin Gene-Related Peptide Biophysics ICL intracellular loop Calcitonin gene-related peptide Article 03 medical and health sciences G protein coupling Animals Humans G protein-coupled receptor Adaptor Proteins Signal Transducing Membrane Proteins Cell Biology GPCR G protein coupled receptor 030104 developmental biology HEK293 Cells Calcitonin RAMP1 HUVECs Human umbilical vein endothelial cells 030217 neurology & neurosurgery |
| Zdroj: | Biochimica et Biophysica Acta. Biomembranes |
| ISSN: | 1879-2642 |
| Popis: | Receptor component protein (RCP) is a 148 amino acid intracellular peripheral membrane protein, previously identified as promoting the coupling of CGRP to cAMP production at the CGRP receptor, a heterodimer of calcitonin receptor like-receptor (CLR), a family B G protein-coupled receptor (GPCR) and receptor activity modifying protein 1 (RAMP1). We extend these observations to show that it selectively enhances CGRP receptor coupling to Gs but not Gq or pERK activation. At other family B GPCRs, it enhances cAMP production at the calcitonin, corticotrophin releasing factor type 1a and glucagon-like peptide type 2 receptors with their cognate ligands but not at the adrenomedullin type 1 (AM1), gastric inhibitory peptide and glucagon-like peptide type 1 receptors, all expressed in transfected HEK293S cells. However, there is also cell-line variability as RCP did not enhance cAMP production at the endogenous calcitonin receptor in HEK293T cells and it has previously been reported that it is active on the AM1 receptor expressed on NIH3T3 cells. RCP appears to behave as a positive allosteric modulator at coupling a number of family B GPCRs to Gs, albeit in a manner that is regulated by cell-specific factors. It may exert its effects at the interface between the 2nd intracellular loop of the GPCR and Gs, although there is likely to be some overlap between this location and that occupied by the C-terminus of RAMPs if they bind to the GPCRs. Graphical abstract Unlabelled Image Highlights • RCP promotes coupling of the CGRP receptor to Gs but not Gi or ERK activation. • RCP enhances Gs coupling for the calcitonin, CRF 1a and GLP-2 receptors. • RCP does not act on adrenomedullin 1, GIP or GLP-1 receptors in HEK293S cells. • The actions of RCP depend on the cell line background. |
| Databáze: | OpenAIRE |
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