EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF

Nature ◽  
10.1038/47260 ◽  
1999 ◽  
Vol 402 (6764) ◽  
pp. 884-888 ◽  
Author(s):  
Norbert Prenzel ◽  
Esther Zwick ◽  
Henrik Daub ◽  
Michael Leserer ◽  
Reimar Abraham ◽  
...  
Keyword(s):  
G Protein ◽  
Egf Receptor ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled ◽  
Receptor Transactivation

scholarly journals The metalloprotease Kuzbanian (ADAM10) mediates the transactivation of EGF receptor by G protein–coupled receptors

2002 ◽  
Vol 158 (2) ◽  
pp. 221-226 ◽  
Author(s):  
Yibing Yan ◽  
Kyoko Shirakabe ◽  
Zena Werb
Keyword(s):  
Signaling Pathways ◽  
G Protein ◽  
Egf Receptor ◽  
Critical Role ◽  
G Protein Coupled Receptors ◽  
Heparin Binding ◽  
Egf Receptors ◽  
Gpcr Activation ◽  
G Protein Coupled ◽  
Stimulation Of

Communication between different signaling pathways enables cells to coordinate the responses to diverse environmental signals. Activation of the transmembrane growth factor precursors plays a critical role in this communication and often involves metalloprotease-mediated proteolysis. Stimulation of G protein–coupled receptors (GPCR) transactivates the EGF receptors (EGFRs), which occurs via a metalloprotease-dependent cleavage of heparin-binding EGF (HB-EGF). However, the metalloprotease mediating the transactivation remains elusive. We show that the integral membrane metalloprotease Kuzbanian (KUZ; ADAM10), which controls Notch signaling in Drosophila, stimulates GPCR transactivation of EGFR. Upon stimulation of the bombesin receptors, KUZ increases the docking and activation of adaptors Src homology 2 domain–containing protein and Gab1 on the EGFR, and activation of Ras and Erk. In contrast, transfection of a protease domain–deleted KUZ, or blocking endogenous KUZ by morpholino antisense oligonucleotides, suppresses the transactivation. The effect of KUZ on shedding of HB-EGF and consequent transactivation of the EGFR depends on its metalloprotease activity. GPCR activation enhances the association of KUZ and its substrate HB-EGF with tetraspanin CD9. Thus, KUZ regulates the relay between the GPCR and EGFR signaling pathways.

ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors

2006 ◽  
Vol 291 (1) ◽  
pp. C1-C10 ◽  
Author(s):  
Haruhiko Ohtsu ◽  
Peter J. Dempsey ◽  
Satoru Eguchi
Keyword(s):  
G Protein ◽  
Egf Receptor ◽  
Current Knowledge ◽  
G Protein Coupled Receptors ◽  
Surface Proteins ◽  
Egf Receptors ◽  
Cellular Functions ◽  
Egfr Transactivation ◽  
And Migration ◽  
G Protein Coupled

A disintegrin and metalloprotease (ADAM) is a membrane-anchored metalloprotease implicated in the ectodomain shedding of cell surface proteins, including the ligands for epidermal growth factor (EGF) receptors (EGFR)/ErbB. It has been well documented that the transactivation of the EGFR plays critical roles for many cellular functions, such as proliferation and migration mediated through multiple G protein-coupled receptors (GPCRs). Recent accumulating evidence has suggested that ADAMs are the key metalloproteases activated by several GPCR agonists to produce a mature EGFR ligand leading to the EGFR transactivation. In this review, we describe the current knowledge on ADAMs implicated in mediating EGFR transactivation. The major focus of the review will be on the possible upstream mechanisms of ADAM activation by GPCRs as well as downstream signal transduction and the pathophysiological significances of ADAM-dependent EGFR transactivation.

scholarly journals Epidermal Growth Factor (EGF) Receptor-dependent ERK Activation by G Protein-coupled Receptors

2001 ◽  
Vol 276 (25) ◽  
pp. 23155-23160 ◽  
Author(s):  
Kristen L. Pierce ◽  
Akira Tohgo ◽  
Seungkirl Ahn ◽  
Michael E. Field ◽  
Louis M. Luttrell ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
G Protein ◽  
Egf Receptor ◽  
G Protein Coupled Receptors ◽  
Erk Activation ◽  
Epidermal Growth ◽  
G Protein Coupled
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