Receptor component protein (RCP): a member of a multi-protein complex required for G-protein-coupled signal transduction

2002 ◽  
Vol 30 (4) ◽  
pp. 460-464 ◽  
Author(s):  
M. A. Prado ◽  
B. Evans-Bain ◽  
I. M. Dickerson
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Signal Transduction Pathway ◽  
Cgrp Receptor ◽  
Receptor Component ◽  
Calcitonin Gene ◽  
Cellular Signal ◽  
Cellular Signal Transduction Pathway ◽  
G Protein Coupled ◽  
Component Protein

The calcitonin-gene-related peptide (CGRP) receptor component protein (RCP) is a 148-amino-acid intracellular protein that is required for G-protein-coupled signal transduction at receptors for the neuropeptide CGRP. RCP works in conjunction with two other proteins to constitute a functional CGRP receptor: calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein 1 (RAMP1).CRLR has the stereotypical seven-transmembrane topology of a G-protein-coupled receptor; it requires RAMP1 for trafficking to the cell surface and for ligand specificity, and requires RCP for coupling to the cellular signal transduction pathway. We have made cell lines that expressed an antisense construct of RCP and determined that CGRP-mediated signal transduction was reduced, while CGRP binding was unaffected. Furthermore, signalling at two other endogenous G-protein-coupled receptors was unaffected, suggesting that RCP was specific for a limited subset of receptors.

scholarly journals The Role of Cgrp-Receptor Component Protein (Rcp) in Cgrp-Mediated Signal Transduction

2001 ◽  
Vol 1 ◽  
pp. 12-12
Author(s):  
M. A. Prado ◽  
B. Evans-Bain ◽  
S. L. Santi ◽  
I. M. Dickerson
Keyword(s):  
Signal Transduction ◽  
Cgrp Receptor ◽  
Nih3t3 Cells ◽  
New Class ◽  
Receptor Component ◽  
Calcitonin Gene ◽  
Cellular Signal ◽  
Signal Transduction Proteins ◽  
Component Protein

The calcitonin gene-related peptide (CGRP)-receptor component protein (RCP) is a 17-kDa intracellular peripheral membrane protein required for signal transduction at CGRP receptors. To determine the role of RCP in CGRP-mediated signal transduction, RCP was depleted from NIH3T3 cells using antisense strategy. Loss of RCP protein correlated with loss of cAMP production by CGRP in the antisense cells. In contrast, loss of RCP had no effect on CGRP-mediated binding; therefore RCP is not acting as a chaperone for the CGRP receptor. Instead, RCP is a novel signal transduction molecule that couples the CGRP receptor to the cellular signal transduction machinery. RCP thus represents a prototype for a new class of signal transduction proteins that are required for regulation of G protein-coupled receptors.

scholarly journals The β-Arrestin-Like Protein Rim8 Is Hyperphosphorylated and Complexes with Rim21 and Rim101 To Promote Adaptation to Neutral-Alkaline pH

2012 ◽  
Vol 11 (5) ◽  
pp. 683-693 ◽  
Author(s):  
Jonathan Gomez-Raja ◽  
Dana A. Davis
Keyword(s):  
Signal Transduction ◽  
Transcription Factor ◽  
G Protein ◽  
Signal Transduction Pathway ◽  
Multivesicular Bodies ◽  
Ph Sensing ◽  
Content Type ◽  
Protein Levels ◽  
G Protein Coupled

ABSTRACTβ-Arrestin proteins are critical for G-protein-coupled receptor desensitization and turnover. However, β-arrestins have recently been shown to play direct roles in nonheterotrimeric G-protein signal transduction. TheCandida albicansβ-arrestin-like protein Rim8 is required for activation of the Rim101 pH-sensing pathway and for pathogenesis. We have found thatC. albicansRim8 is posttranslationally modified by phosphorylation and specific phosphorylation states are associated with activation of the pH-sensing pathway. Rim8 associated with both the receptor Rim21 and the transcription factor Rim101, suggesting that Rim8 bridges the signaling and activation steps of the pathway. Finally, upon activation of the Rim101 transcription factor,C. albicansRim8 was transcriptionally repressed and Rim8 protein levels were rapidly reduced. Our studies suggest that Rim8 is taken up into multivesicular bodies and degraded within the vacuole. In total, our results reveal a novel mechanism for tightly regulating the activity of a signal transduction pathway. Although the role of β-arrestin proteins in mammalian signal transduction pathways has been demonstrated, relatively little is known about how β-arrestins contribute to signal transduction. Our analyses provide some insights into potential roles.

The role of the CGRP-receptor component protein (RCP) in adrenomedullin receptor signal transduction

Peptides ◽  
2001 ◽  
Vol 22 (11) ◽  
pp. 1773-1781 ◽  
Author(s):  
Marya A Prado ◽  
Bornadata Evans-Bain ◽  
Kevin R Oliver ◽  
Ian M Dickerson
Keyword(s):  
Signal Transduction ◽  
Cgrp Receptor ◽  
Receptor Signal ◽  
Receptor Component ◽  
Adrenomedullin Receptor ◽  
Component Protein

scholarly journals Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies

2013 ◽  
Vol 10 (79) ◽  
pp. 20120846 ◽  
Author(s):  
Shabana Vohra ◽  
Bruck Taddese ◽  
Alex C. Conner ◽  
David R. Poyner ◽  
Debbie L. Hay ◽  
...  
Keyword(s):  
G Protein ◽  
Calcitonin Gene Related Peptide ◽  
G Protein Coupled Receptors ◽  
Cgrp Receptor ◽  
Conserved Residues ◽  
Related Peptide ◽  
Class A ◽  
Calcitonin Gene ◽  
Class B ◽  
G Protein Coupled

Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A–class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg 2.39 , His 2.43 and Glu 3.46 , which makes a polar lock with T 6.37 . These alignments and models provide useful tools for understanding class B GPCR function.

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