Identification and characterization of human PEIG-1/GPRC5A as a 12-Otetradecanoyl phorbol-13-acetate (TPA) and PKC-induced gene

Abstract: Homo sapiens orphan G protein-coupling receptor PEIG-1 was first cloned and characterized by applying differential display to T84 colonic carcinoma cells incubated in the presence of phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (GenBank AF506289.1). Later, Lotan's laborat...

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Autores principales: Mori, Consuelo, Valdivieso, Ángel Gabriel, Clauzure, Mariángeles, Massip Copiz, María M., Aguilar, María Á., Cafferata, Eduardo G.A., Santa Coloma, Tomás Antonio
Formato: Artículo
Lenguaje:Inglés
Publicado: Elsevier 2022
Materias:
PKC
TPA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/14592
Aporte de:
id I33-R139-123456789-14592
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic GPRC5A
PEIG-1
PKC
RAI3
RAID-1
TIG1
TPA
spellingShingle GPRC5A
PEIG-1
PKC
RAI3
RAID-1
TIG1
TPA
Mori, Consuelo
Valdivieso, Ángel Gabriel
Clauzure, Mariángeles
Massip Copiz, María M.
Aguilar, María Á.
Cafferata, Eduardo G.A.
Santa Coloma, Tomás Antonio
Identification and characterization of human PEIG-1/GPRC5A as a 12-Otetradecanoyl phorbol-13-acetate (TPA) and PKC-induced gene
topic_facet GPRC5A
PEIG-1
PKC
RAI3
RAID-1
TIG1
TPA
description Abstract: Homo sapiens orphan G protein-coupling receptor PEIG-1 was first cloned and characterized by applying differential display to T84 colonic carcinoma cells incubated in the presence of phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (GenBank AF506289.1). Later, Lotan's laboratory found the same gene product in response to retinoic acid analogues, naming it with the symbol RAIG1. Now the official HGNC symbol is GPRC5A. Here, we report the extension of its original cDNA fragment towards the 5' and 3' end. In addition, we show that TPA (100 ng/ml, 162 nM) strongly stimulated GPRC5A mRNA in T84 colonic carcinoma cells, with maximal expression at 4 h and 100 ng/ml (162 nM). Western blots showed several bands between 35 and 50 kDa, responding to TPA stimulation. Confocal microscopy confirmed its TPA upregulation and the location in the plasma membrane. The PKC inhibitor Gö 6983 (10 μM), and the Ca2+ chelator BAPTA-AM (150 μM), strongly inhibited its TPA induced upregulation. The PKA inhibitor H-89 (10 μM), and the MEK1/2 inhibitor U0126 (10 μM), also produced a significant reduction in the TPA response (~50%). The SGK1 inhibitor GSK650394 stimulated GPRC5A basal levels at low doses and inhibit its TPA-induced expression at concentrations ≥10 μM. The IL-1β autocrine loop and downstream signalling did not affect its expression. In conclusion, RAIG1/RAI3/GPRC5A corresponds to the originally reported PEIG-1/TIG1; the inhibition observed in the presence of Gö 6983, BAPTA and U0126, suggests that its TPA-induced upregulation is mediated through a PKC/Ca2+ →MEK1/2 signalling axis. PKA and SGK1 kinases are also involved in its TPA-induced upregulation.
format Artículo
author Mori, Consuelo
Valdivieso, Ángel Gabriel
Clauzure, Mariángeles
Massip Copiz, María M.
Aguilar, María Á.
Cafferata, Eduardo G.A.
Santa Coloma, Tomás Antonio
author_facet Mori, Consuelo
Valdivieso, Ángel Gabriel
Clauzure, Mariángeles
Massip Copiz, María M.
Aguilar, María Á.
Cafferata, Eduardo G.A.
Santa Coloma, Tomás Antonio
author_sort Mori, Consuelo
title Identification and characterization of human PEIG-1/GPRC5A as a 12-Otetradecanoyl phorbol-13-acetate (TPA) and PKC-induced gene
title_short Identification and characterization of human PEIG-1/GPRC5A as a 12-Otetradecanoyl phorbol-13-acetate (TPA) and PKC-induced gene
title_full Identification and characterization of human PEIG-1/GPRC5A as a 12-Otetradecanoyl phorbol-13-acetate (TPA) and PKC-induced gene
title_fullStr Identification and characterization of human PEIG-1/GPRC5A as a 12-Otetradecanoyl phorbol-13-acetate (TPA) and PKC-induced gene
title_full_unstemmed Identification and characterization of human PEIG-1/GPRC5A as a 12-Otetradecanoyl phorbol-13-acetate (TPA) and PKC-induced gene
title_sort identification and characterization of human peig-1/gprc5a as a 12-otetradecanoyl phorbol-13-acetate (tpa) and pkc-induced gene
publisher Elsevier
publishDate 2022
url https://repositorio.uca.edu.ar/handle/123456789/14592
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