A comparative study of growth factor receptor and G-protein-coupled receptor phosphoinositide and Ca2+ signalling in SH-SY5Y neuroblastoma cells

1999 ◽  
Vol 27 (1) ◽  
pp. A34-A34
Author(s):  
L.M. Wheldon ◽  
P.J. White ◽  
S.R. Nahorski ◽  
G.B. Willars
Keyword(s):  
Growth Factor ◽  
Comparative Study ◽  
G Protein ◽  
Neuroblastoma Cells ◽  
Growth Factor 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 The Platelet-derived Growth Factor Receptor-β Phosphorylates and Activates G Protein-coupled Receptor Kinase-2

2005 ◽  
Vol 280 (35) ◽  
pp. 31027-31035 ◽  
Author(s):  
Jiao-Hui Wu ◽  
Robi Goswami ◽  
Luke K. Kim ◽  
William E. Miller ◽  
Karsten Peppel ◽  
...  
Keyword(s):  
Growth Factor ◽  
G Protein ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals G protein–coupled receptor kinase 2 (GRK2) is localized to centrosomes and mediates epidermal growth factor–promoted centrosomal separation

2013 ◽  
Vol 24 (18) ◽  
pp. 2795-2806 ◽  
Author(s):  
Christopher H. So ◽  
Allison Michal ◽  
Konstantin E. Komolov ◽  
Jiansong Luo ◽  
Jeffrey L. Benovic
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
G Protein ◽  
Growth Factor Receptor ◽  
Dominant Negative ◽  
G Protein Coupled Receptor ◽  
Microtubule Nucleation ◽  
Epidermal Growth ◽  
G Protein Coupled

G protein–coupled receptor kinases (GRKs) play a central role in regulating receptor signaling, but recent studies suggest a broader role in modulating normal cellular functions. For example, GRK5 has been shown to localize to centrosomes and regulate microtubule nucleation and cell cycle progression. Here we demonstrate that GRK2 is also localized to centrosomes, although it has no role in centrosome duplication or microtubule nucleation. Of interest, knockdown of GRK2 inhibits epidermal growth factor receptor (EGFR)–mediated separation of duplicated centrosomes. This EGFR/GRK2-mediated process depends on the protein kinases mammalian STE20-like kinase 2 (Mst2) and Nek2A but does not involve polo-like kinase 1. In vitro analysis and dominant-negative approaches reveal that GRK2 directly phosphorylates and activates Mst2. Collectively these findings demonstrate that GRK2 is localized to centrosomes and plays a central role in mitogen-promoted centrosome separation most likely via its ability to phosphorylate Mst2.

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