scholarly journals Arachidonic acid induces ERK activation via Src SH2 domain association with the epidermal growth factor receptor

2006 ◽  
Vol 69 (10) ◽  
pp. 1823-1832 ◽  
Author(s):  
L.D. Alexander ◽  
Y. Ding ◽  
S. Alagarsamy ◽  
X.-L. Cui ◽  
J.G. Douglas
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Arachidonic Acid ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Sh2 Domain ◽  
Erk Activation ◽  
Epidermal Growth

scholarly journals The phosphotyrosine interaction domain of Shc binds an LXNPXY motif on the epidermal growth factor receptor.

1995 ◽  
Vol 15 (8) ◽  
pp. 4403-4409 ◽  
Author(s):  
A G Batzer ◽  
P Blaikie ◽  
K Nelson ◽  
J Schlessinger ◽  
B Margolis
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Sh2 Domain ◽  
Interaction Domain ◽  
Competition Analysis ◽  
Amino Terminal ◽  
Epidermal Growth ◽  
Domain Protein

Shc is an SH2 domain protein that is tyrosine phosphorylated in cells stimulated with a variety of growth factors and cytokines. Once phosphorylated, Shc binds the Grb2-Sos complex, leading to Ras activation. Shc can interact with tyrosine-phosphorylated proteins by binding to phosphotyrosine in the context of an NPXpY motif, where pY is a phosphotyrosine. This is an unusual binding site for an SH2 domain protein whose binding specificity is usually controlled by residues carboxy terminal, not amino terminal, to the phosphotyrosine. Recently we identified a second region in Shc, named the phosphotyrosine interaction (PI) domain, and we have found it to be present in a variety of other cellular proteins. In this study we used a dephosphorylation protection assay, competition analysis with phosphotyrosine-containing synthetic peptides, and epidermal growth factor receptor (EGFR) mutants to determine the binding sites of the PI domain of Shc on the EGFR. We demonstrate that the PI domain of Shc binds the LXNPXpY motif that encompasses Y-1148 of the activated EGFR. We conclude that the PI domain imparts to Shc its ability to bind the NPXpY motif.

scholarly journals Frustration of endocytosis potentiates compression-induced receptor signaling

2020 ◽  
Vol 133 (17) ◽  
pp. jcs239681 ◽  
Author(s):  
Francesco Baschieri ◽  
Dahiana Le Devedec ◽  
Samuel Tettarasar ◽  
Nadia Elkhatib ◽  
Guillaume Montagnac
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Membrane Tension ◽  
Mechanical Perturbation ◽  
Erk Activation ◽  
Epidermal Growth ◽  
Paracrine Activation ◽  
Dynamic Exchange

ABSTRACTCells experience mechanical stresses in different physiological and pathological settings. Clathrin-coated structures (CCSs) are sensitive to such perturbations in a way that often results in a mechanical impairment of endocytic budding. Compressive stress is a mechanical perturbation that leads to increased membrane tension and promotes proliferative signals. Here, we report that compression leads to frustration of CCSs and that CCSs are required to potentiate receptor-mediated signaling in these conditions. We show that cell compression stalled CCS dynamics and slowed down the dynamic exchange of CCS components. As previously reported, compression-induced paracrine activation of the epidermal growth factor receptor (EGFR) was the primary cause of ERK (ERK1 and ERK2, also known as MAPK3 and MAPK1, respectively) activation in these conditions. We observed that EGFR was efficiently recruited at CCSs upon compression and that CCSs were required for full ERK activation. In addition, we demonstrated that compression-induced frustrated CCSs could also increase ligand-dependent signaling of other receptors. We thus propose that CCS frustration resulting from mechanical perturbations can potentiate signaling through different receptors, with potential important consequences for the adaptation of the cell to its environment.This article has an associated First Person interview with the first author of the paper.

Identification of Amino Acids in the N-Terminal SH2 Domain of Phospholipase C.gamma.1 Important in the Interaction with Epidermal Growth Factor Receptor

Biochemistry ◽  
1994 ◽  
Vol 33 (49) ◽  
pp. 14671-14678 ◽  
Author(s):  
James R. Gergel ◽  
Dennis J. McNamara ◽  
Ellen M. Dobrusin ◽  
Guochang Zhu ◽  
Alan R. Saltiel ◽  
...  
Keyword(s):  
Amino Acids ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Sh2 Domain ◽  
Epidermal Growth
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