scholarly journals Mitosis-specific Negative Regulation of Epidermal Growth Factor Receptor, Triggered by a Decrease in Ligand Binding and Dimerization, Can Be Overcome by Overexpression of Receptor

1997 ◽  
Vol 272 (30) ◽  
pp. 18656-18665 ◽  
Author(s):  
Nobutaka Kiyokawa ◽  
Eun Kyung Lee ◽  
Devarajan Karunagaran ◽  
Shiaw-Yih Lin ◽  
Mien-Chie Hung
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Ligand Binding ◽  
Growth Factor Receptor ◽  
Negative Regulation ◽  
Epidermal Growth

Ligand binding induces a conformational change in epidermal growth factor receptor dimers

2012 ◽  
Vol 30 (6) ◽  
pp. 394-409 ◽  
Author(s):  
Francesca Walker ◽  
Julie Rothacker ◽  
Christine Henderson ◽  
Edouard C. Nice ◽  
Bruno Catimel ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Ligand Binding ◽  
Conformational Change ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Receptor Dimers

scholarly journals Positive and negative tissue-specific signaling by a nematode epidermal growth factor receptor.

1997 ◽  
Vol 8 (5) ◽  
pp. 779-793 ◽  
Author(s):  
G M Lesa ◽  
P W Sternberg
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Binding Sites ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Negative Regulation ◽  
Tissue Specific ◽  
Epidermal Growth

The major determinants of receptor tissue tyrosine kinase (RTK) signaling specificity have been proposed to be Src homology 2 (SH2) binding sites, phosphotyrosine-containing oligopeptides in the cytoplasmic domain of the receptor. The Caenorhabditis elegans epidermal growth factor receptor homologue LET-23 has multiple functions during development and has eight potential SH2-binding sites in a region carboxyl terminal to its kinase domain. By analyzing transgenic nematodes for three distinct LET-23 functions, we show that six of eight potential sites function in vivo and that they are required for most, but not all, of LET-23 activity. A single site is necessary and sufficient to promote wild-type fertility. Three other sites activate the RAS pathway and are involved only in viability and vulval differentiation. A fifth site is promiscuous and can mediate all three LET-23 functions. An additional site mediates tissue-specific negative regulation. Putative SH2 binding sites are thus key effectors of both cell-specific and negative regulation in an intact organism. We suggest two distinct mechanisms for tissue-specific RTK-mediated signaling. A positive mechanism would promote RTK function through effectors present only in certain cell types. A negative mechanism would inhibit RTK function through tissue-specific negative regulators.

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