scholarly journals Systems Biological Analysis of Epidermal Growth Factor Receptor Internalization Dynamics for Altered Receptor Levels

2009 ◽  
Vol 284 (25) ◽  
pp. 17243-17252 ◽  
Author(s):  
Hannah Schmidt-Glenewinkel ◽  
Eileen Reinz ◽  
Roland Eils ◽  
Nathan R. Brady
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Internalization ◽  
Biological Analysis ◽  
Epidermal Growth

A Conjugate of an Anti-Epidermal Growth Factor Receptor (EGFR) VHH and a Cell-Penetrating Peptide Drives Receptor Internalization and Blocks EGFR Activation

ChemBioChem ◽  
2017 ◽  
Vol 18 (24) ◽  
pp. 2390-2394 ◽  
Author(s):  
Sanne A. M. van Lith ◽  
Dirk van den Brand ◽  
Rike Wallbrecher ◽  
Sander M. J. van Duijnhoven ◽  
Roland Brock ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Internalization ◽  
Cell Penetrating Peptide ◽  
Egfr Activation ◽  
Cell Penetrating ◽  
A Cell ◽  
Epidermal Growth

scholarly journals Alix/AIP1 Antagonizes Epidermal Growth Factor Receptor Downregulation by the Cbl-SETA/CIN85 Complex

2004 ◽  
Vol 24 (20) ◽  
pp. 8981-8993 ◽  
Author(s):  
Mirko H. H. Schmidt ◽  
Daniela Hoeller ◽  
Jiuhong Yu ◽  
Frank B. Furnari ◽  
Webster K. Cavenee ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Internalization ◽  
Interacting Protein ◽  
Low Intensity ◽  
C Terminus ◽  
Epidermal Growth ◽  
Interfering Rna

ABSTRACT The assembly of the Cbl-SETA/CIN85-endophilin complex at the C terminus of the epidermal growth factor receptor (EGFR) following ligand activation mediates its internalization and ubiquitination. We found that the SETA/CIN85-interacting protein Alix/AIP1, which also binds endophilins, modulates this complex. Alix was found to associate indirectly with EGFR, regardless of its activation state, and with ΔEGFR, which signals at low intensity and does not bind Cbls or SETA/CIN85. In agreement with this, Alix interaction did not occur via SETA/CIN85. However, SETA/CIN85 and Alix were capable of mutually promoting their interaction with the EGFR. Increasing the level of Alix weakened the interaction between SETA/CIN85 and Cbl and reduced the tyrosine phosphorylation of c-Cbl and the level of ubiquitination of EGFR, SETA/CIN85, and Cbls. This antagonism of the Cbl-SETA/CIN85 complex by Alix was reflected in its diminution of EGFR internalization. In agreement with this, small interfering RNA-mediated knockdown of Alix promoted EGFR internalization and downregulation. It has been suggested that SETA/CIN85 promotes receptor internalization by recruiting endophilins. However, Alix was also capable of increasing the level of endophilin associated with EGFR, implying that this is not sufficient to promote receptor internalization. We propose that Alix inhibits EGFR internalization by attenuating the interaction between Cbl and SETA/CIN85 and by inhibiting Cbl-mediated ubiquitination of the EGFR.

scholarly journals Eps15 Is Recruited to the Plasma Membrane upon Epidermal Growth Factor Receptor Activation and Localizes to Components of the Endocytic Pathway during Receptor Internalization

1999 ◽  
Vol 10 (2) ◽  
pp. 417-434 ◽  
Author(s):  
Maria Rosaria Torrisi ◽  
Lavinia Vittoria Lotti ◽  
Francesca Belleudi ◽  
Roberto Gradini ◽  
Anna Elisabetta Salcini ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Plasma Membrane ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Adaptor Protein ◽  
Receptor Activation ◽  
Endocytic Pathway ◽  
Receptor Internalization ◽  
Epidermal Growth

Eps15 is a substrate for the tyrosine kinase of the epidermal growth factor receptor (EGFR) and is characterized by the presence of a novel protein:protein interaction domain, the EH domain. Eps15 also stably binds the clathrin adaptor protein complex AP-2. Previous work demonstrated an essential role for eps15 in receptor-mediated endocytosis. In this study we show that, upon activation of the EGFR kinase, eps15 undergoes dramatic relocalization consisting of 1) initial relocalization to the plasma membrane and 2) subsequent colocalization with the EGFR in various intracellular compartments of the endocytic pathway, with the notable exclusion of coated vesicles. Relocalization of eps15 is independent of its binding to the EGFR or of binding of the receptor to AP-2. Furthermore, eps15 appears to undergo tyrosine phosphorylation both at the plasma membrane and in a nocodazole-sensitive compartment, suggesting sustained phosphorylation in endocytic compartments. Our results are consistent with a model in which eps15 undergoes cycles of association:dissociation with membranes and suggest multiple roles for this protein in the endocytic pathway.

scholarly journals Phosphatidylinositol-4-phosphate 5-Kinase-1β Is Essential for Epidermal Growth Factor Receptor-mediated Endocytosis

2001 ◽  
Vol 276 (50) ◽  
pp. 47212-47216 ◽  
Author(s):  
M. Alejandro Barbieri ◽  
Colin M. Heath ◽  
Elizabeth M. Peters ◽  
Alan Wells ◽  
J. Nathan Davis ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Membrane Trafficking ◽  
Growth Factor Receptor ◽  
Receptor Internalization ◽  
Receptor Mediated Endocytosis ◽  
Egfr Expression ◽  
Epidermal Growth ◽  
Phosphatidylinositol 4

Phosphatidylinositol-4,5-bisphosphate (PIP2) is known to play an important role in signal transduction and membrane trafficking. We show that one enzyme responsible for PIP2production, phosphatidylinositol-4-phosphate 5-kinase type 1β (PIPKβ), is essential for epidermal growth factor receptor (EGFR)-mediated endocytosis. Expression of murine PIPKβ in NR6 cells expressing EGFR strikingly increased receptor internalization. Moreover, the kinase was shown to form an immunoprecipitable complex with EGFR. Expression of either a truncated kinase or a kinase dead mutant inhibited EGFR endocytosis and also blocked the membrane recruitment of PIPKβ and both clathrin light chain and dynamin. Our results delineate a novel mechanism by which PIPKβ regulates receptor-mediated endocytosis and receptor tyrosine kinase membrane traffic.

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