scholarly journals Shedding of c-Met is regulated by crosstalk between a G-protein coupled receptor and the EGF receptor and is mediated by a TIMP-3 sensitive metalloproteinase

2014 ◽  
Vol 127 (7) ◽  
pp. 1620-1620 ◽  
Author(s):  
D. Nath ◽  
N. J. Williamson ◽  
R. Jarvis ◽  
G. Murphy
Keyword(s):  
G Protein ◽  
Egf Receptor ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Shedding of c-Met is regulated by crosstalk between a G-protein coupled receptor and the EGF receptor and is mediated by a TIMP-3 sensitive metalloproteinase

2001 ◽  
Vol 114 (6) ◽  
pp. 1213-1220
Author(s):  
D. Nath ◽  
N.J. Williamson ◽  
R. Jarvis ◽  
G. Murphy
Keyword(s):  
Growth Factor ◽  
G Protein ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Ectodomain Shedding ◽  
G Protein Coupled Receptor ◽  
Cell Matrix ◽  
Cell Matrix Interactions ◽  
G Protein Coupled

A wide repertoire of transmembrane proteins are proteolytically released from the cell surface by a process known as ‘ectodomain shedding’, under both normal and pathophysiological conditions. Little is known about the physiological mechanisms that regulate this process. As a model system, we have investigated the metalloproteinase-mediated cleavage of the hepatocyte growth factor receptor, Met. We show that epidermal growth factor (EGF) receptor activation, either directly by EGF or indirectly via the G-protein coupled receptor (GPCR) agonist lysophosphatidic acid (LPA), induces cleavage of Met through activation of the Erk MAP kinase signalling cascade. The tyrosine kinase activity of the EGFR was a prerequisite for this stimulation, since treatment of cells with a synthetic inhibitor of this receptor, AG1478, completely abrogated shedding. The metalloproteinase mediating Met cleavage was specifically inhibited by the tissue inhibitor of metalloproteinases (TIMP)-3, but not by TIMP-1 or TIMP-2. Furthermore, the level of Met shedding could be modulated by different cell-matrix interactions. Our results indicate that ectodomain shedding is a highly regulated process that can be stimulated by EGFR signalling pathways and integrin ligation.

scholarly journals Estrogen Action Via the G Protein-Coupled Receptor, GPR30: Stimulation of Adenylyl Cyclase and cAMP-Mediated Attenuation of the Epidermal Growth Factor Receptor-to-MAPK Signaling Axis

2002 ◽  
Vol 16 (1) ◽  
pp. 70-84 ◽  
Author(s):  
Edward J. Filardo ◽  
Jeffrey A. Quinn ◽  
A. Raymond Frackelton ◽  
Kirby I. Bland
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Egf Receptor ◽  
G Protein Coupled Receptor ◽  
Estrogen Action ◽  
Epidermal Growth ◽  
G Protein Coupled ◽  
Stimulation Of

Abstract Estrogen triggers rapid yet transient activation of the MAPKs, extracellular signal-regulated kinase (Erk)-1 and Erk-2. We have reported that this estrogen action requires the G protein-coupled receptor, GPR30, and occurs via Gβγ-subunit protein-dependent transactivation of the epidermal growth factor (EGF) receptor through the release of pro-heparan-bound EGF from the cell surface. Here we investigate the mechanism by which Erk-1/-2 activity is rapidly restored to basal levels after estrogen stimulation. Evidence is provided that attenuation of Erk-1/-2 activity by estrogen occurs via GPR30-dependent stimulation of adenylyl cyclase and cAMP-dependent signaling that results in Raf-1 inactivation. We show that 17β-E2 represses EGF-induced activation of the Raf-to-Erk pathway in human breast carcinoma cells that express GPR30, including MCF-7 and SKBR3 cells which express both or neither, ER, respectively. MDA-MB-231 cells, which express ERβ, but not ERα, and low levels of GPR30 protein, are unable to stimulate adenylyl cyclase or promote estrogen-mediated blockade of EGF-induced activation of Erk-1/-2. Pretreatment of MDA-MB-231 cells with cholera toxin, which ADP-ribosylates and activates Gαs subunit proteins, results in G protein-coupled receptor (GPCR)-independent adenylyl cyclase activity and suppression of EGF-induced Erk-1/-2 activity. Transfection of GPR30 into MDA-MB-231 cells restores their ability to stimulate adenylyl cyclase and attenuate EGF-induced activation of Erk-1/-2 by estrogen. Moreover, GPR30-dependent, cAMP-mediated attenuation of EGF-induced Erk-1/-2 activity was achieved by ER antagonists such as tamoxifen or ICI 182, 780; yet not by 17α-E2 or progesterone. Thus, our data delineate a novel mechanism, requiring GPR30 and estrogen, that acts to regulate Erk-1/-2 activity via an inhibitory signal mediated by cAMP. Coupled with our prior findings, these current data imply that estrogen balances Erk-1/-2 activity through a single GPCR via two distinct G protein-dependent signaling pathways that have opposing effects on the EGF receptor-to-MAPK pathway.

Vanadium compounds cause activation of G protein-coupled receptor signaling

2020 ◽  
Author(s):  
Debbie C. Crans ◽  
Duaa Althumairy ◽  
Heide Murakami ◽  
B. George Barisas ◽  
Deborah Roess
Keyword(s):  
G Protein ◽  
Receptor Signaling ◽  
G Protein Coupled Receptor ◽  
Vanadium Compounds ◽  
G Protein Coupled
Sign in / Sign up

Export Citation Format

Share Document