Lysosomal targeting of epidermal growth factor receptors via a kinase-dependent pathway is mediated by the receptor carboxyl-terminal residues 1022-1123.

The Journal of Biological Chemistry
E S KornilovaA Sorkin

Abstract

Binding of epidermal growth factor (EGF) to its receptor induces rapid internalization and degradation of both ligand and receptor via the lysosomal pathway. To study the mechanism of intracellular sorting of EGF-EGF receptor complexes to lysosomes, NIH 3T3 cells transfected with wild-type and mutant EGF receptors were employed. The kinetics of 125I-EGF trafficking was analyzed using low concentrations of the ligand to avoid saturation of the specific sorting system. The relative size of the pool of internalized 125I-EGF-receptor complexes that were capable of recycling decreased as receptors traversed the endosomal system. The rate of 125I-EGF sequestration from the recycling pathway correlated with the rate of 125I-EGF transition from early to late endosomes as measured by Percoll gradient fractionation. Deletion of the last 63 amino acids of the EGF receptor cytoplasmic tail did not inhibit the process of sequestration and targeting to the late endosomes and lysosomes. Truncation of the 123 residues, however, resulted in impaired lysosomal targeting and increased recycling of EGF. Receptor mutant in which 165 residues were deleted displayed maximal ability to recycle and a minimal extent of sorting to the late endosomes. The...Continue Reading

References

Nov 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·J A McKannaS Cohen
Apr 1, 1992·The Journal of Cell Biology·S FelderJ Schlessinger
Mar 28, 1989·Biochimica Et Biophysica Acta·A SorkinN Nikolsky
Jan 1, 1985·Journal of Cellular Physiology·R M LyallM C Willingham
Apr 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·L BeguinotI Pastan
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·K J CokerC A Guyer
Jun 1, 1993·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·A Sorkin, C M Waters
Mar 15, 1996·Science·P De CamilliP Novick
Nov 8, 1996·Science·M A NowakA J McMichael
Jul 1, 1991·Trends in Cell Biology·G Griffiths, J Gruenberg

❮ Previous
Next ❯

Citations

Feb 15, 2001·Biopolymers·K ChaturvediR D Howells
Feb 16, 2000·Biochemical and Biophysical Research Communications·B P KeeganS W Spaulding
Jun 23, 2006·Breast Cancer Research and Treatment·Diane PalmieriPatricia S Steeg
Nov 5, 2003·Advanced Drug Delivery Reviews·Richard C Kurten
Nov 10, 2000·Advanced Drug Delivery Reviews·R J Parkes, S L Hart
Aug 15, 2002·Biochimica Et Biophysica Acta·Anja ten BrinkeJoseph J Batenburg
Nov 22, 2011·The Journal of Biological Chemistry·Jamie S RushBrian P Ceresa
Mar 7, 2009·The Journal of Biological Chemistry·Phillip A Vanlandingham, Brian P Ceresa
Apr 16, 2002·Molecular Biology of the Cell·Martin SachseJudith Klumperman
Nov 17, 1999·Molecular Biology of the Cell·R PrekerisR H Scheller
Oct 8, 2004·Molecular Biology of the Cell·Cheri S LazarGordon N Gill
Feb 17, 2001·American Journal of Respiratory and Critical Care Medicine·K TakeyamaJ A Nadel
Feb 15, 2002·Biological Chemistry·P O HackelA Ullrich
Apr 17, 2001·Biochemical and Biophysical Research Communications·K SakaguchiM Kasuga
Sep 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Kaisa HaglundIvan Dikic
Jul 18, 2009·Cellular and Molecular Life Sciences : CMLS·Kyu Young SongHorace H Loh
Jun 30, 2006·Experimental Cell Research·Maria L JaramilloMaureen O'Connor McCourt
Oct 27, 2009·Virology·Olivier PernetRobin Buckland
Aug 13, 2013·Molecular and Cellular Endocrinology·Jamie S Rush, Brian P Ceresa
Sep 15, 2012·Biochimica Et Biophysica Acta·Mariarosa A B MeloneGianfranco Peluso
Sep 12, 2003·Developmental Cell·Maya ShellyYosef Yarden
Jun 25, 2008·Biochimica Et Biophysica Acta·Véronique Freund-Michel, Nelly Frossard
Sep 26, 2003·Biophysical Journal·Bart S HendriksDouglas Lauffenburger
Aug 3, 2002·Nature Reviews. Molecular Cell Biology·Alexander Sorkin, Mark Von Zastrow
Oct 3, 1999·The Journal of Biological Chemistry·R JockersS Marullo
Mar 11, 2018·The Journal of Biological Chemistry·Julie A GosneyBrian P Ceresa
Jan 2, 2004·The Journal of Biological Chemistry·Willem StoorvogelPaul M P van Bergen en Henegouwen
May 22, 2016·Journal of Cell Science·John P ChamberlandBrigitte Ritter

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.