Surviving cell death through epidermal growth factor (EGF) signal transduction pathways: Implications for cancer therapy

2006 ◽  
Vol 18 (12) ◽  
pp. 2089-2097 ◽  
Author(s):  
Elizabeth S. Henson ◽  
Spencer B. Gibson
Keyword(s):  
Signal Transduction ◽  
Cell Death ◽  
Growth Factor ◽  
Cancer Therapy ◽  
Epidermal Growth Factor ◽  
Signal Transduction Pathways ◽  
Epidermal Growth

scholarly journals Endosomal Signaling of Epidermal Growth Factor Receptor Stimulates Signal Transduction Pathways Leading to Cell Survival

2002 ◽  
Vol 22 (20) ◽  
pp. 7279-7290 ◽  
Author(s):  
Yi Wang ◽  
Steven Pennock ◽  
Xinmei Chen ◽  
Zhixiang Wang
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Kinase Inhibitor ◽  
Nucleation Site ◽  
Signal Transduction Pathways ◽  
Egfr Signaling ◽  
Endosomal Signaling ◽  
Epidermal Growth

ABSTRACT In spite of intensified efforts to understand cell signaling from endosomes, there is no direct evidence demonstrating that endosomal signaling is sufficient to activate signal transduction pathways and no evidence to demonstrate that endosomal signaling is able to produce a biological outcome. The lack of breakthrough is due in part to the lack of means to generate endosomal signals without plasma membrane signaling. In this paper, we report the establishment of a system to specifically activate epidermal growth factor (EGF) receptor (EGFR) when it endocytoses into endosomes. We treated cells with EGF in the presence of AG-1478, a specific EGFR tyrosine kinase inhibitor, and monensin, which blocks the recycling of EGFR. This treatment led to the internalization of nonactivated EGF-EGFR complexes into endosomes. The endosome-associated EGFR was then activated by removing AG-1478 and monensin. During this procedure we did not observe any surface EGFR phosphorylation. We also achieved specific activation of endosome-associated EGFR without using monensin. By using this system, we provided original evidence demonstrating that (i) the endosome can serve as a nucleation site for the formation of signaling complexes, (ii) endosomal EGFR signaling is sufficient to activate the major signaling pathways leading to cell proliferation and survival, and (iii) endosomal EGFR signaling is sufficient to suppress apoptosis induced by serum withdrawal.

Endosomes, receptor tyrosine kinase internalization and signal transduction

1995 ◽  
Vol 15 (6) ◽  
pp. 411-418 ◽  
Author(s):  
John J. M. Bergeron ◽  
G. M. Di Guglielmo ◽  
Patricia C. Baass ◽  
François Authier ◽  
Barry I. Posner
Keyword(s):  
Signal Transduction ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Receptor Internalization ◽  
Signal Transduction Pathways ◽  
Liver Parenchymal ◽  
Epidermal Growth ◽  
Isolated Liver

Upon the binding of insulin or epidermal growth factor to their cognate receptors on the liver parenchymal plasmalemma, signal transduction and receptor internalization are near co-incident. Indeed, the rapidity and extent; of ligand mediated receptor internalization into endosomes in liver as well as other organs predicts that signal transduction is regulated at this intracellular locus. Although internalization has been thought as a mechanism to attenuate ligand mediated signal transduction responses, detailed studies of internalized receptors in isolated liver endosomes suggest an alternative scenario whereby selective signal transduction pathways can be accessed at this locus.

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