Journal Article
. 1996 Mar; 271(9):5251-7.
doi: 10.1074/jbc.271.9.5251.

All ErbB receptors other than the epidermal growth factor receptor are endocytosis impaired

J Baulida 1 M H Kraus  M Alimandi  P P Di Fiore  G Carpenter  
Affiliations
  • PMID: 8617810
  •     134 citations

Abstract

Four transmembrane tyrosine kinases constitute the ErbB receptor family: the epidermal growth factor (EGF) receptor, ErbB-2, ErbB-3, and ErbB-4. We have measured the endocytic capacities of all four members of the EGF receptor family, including ErbB-3 and ErbB-4, which have not been described previously. EGF-responsive chimeric receptors containing the EGF receptor extracellular domain and different ErbB cytoplasmic domains (EGFR/ErbB) have been employed. The capacity of these growth factor-receptor complexes to mediate 125I-EGF internalization, receptor down-regulation, receptor degradation, and receptor co-immunoprecipitation with AP-2 was assayed. In contrast to the EGF receptor, all EGFR/ErbB receptors show impaired ligand-induced rapid internalization, down-regulation, degradation, and AP-2 association. Also, we have analyzed the heregulin-responsive wild-type ErbB-4 receptor, which does not mediate the rapid internalization of 125I-heregulin, demonstrates no heregulin-regulated receptor degradation, and fails to form association complexes with AP-2. Despite the substantial differences in ligand-induced receptor trafficking between the EGF and ErbB-4 receptors, EGF and heregulin have equivalent capacities to stimulate DNA synthesis in quiescent cells. These results show that the ligand-dependent down-regulation mechanism of the EGF receptor, surprisingly, is not a property of any other known ErbB receptor family member. Since endocytosis is thought to be an attenuation mechanism for growth factor-receptor complexes, these data imply that substantial differences in attenuation mechanisms exist within one family of structurally related receptors.

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Oncotarget, 2014 Sep 25; 5(18). PMID: 25249538    Free PMC article.
Role of Erbin in ErbB2-dependent breast tumor growth.
Yanmei Tao, Chengyong Shen, +13 authors, Lin Mei.
Proc Natl Acad Sci U S A, 2014 Oct 08; 111(42). PMID: 25288731    Free PMC article.
A HER2-specific Modified Fc Fragment (Fcab) Induces Antitumor Effects Through Degradation of HER2 and Apoptosis.
Kin-Mei Leung, Sarah Batey, +16 authors, Haijun Sun.
Mol Ther, 2015 Aug 04; 23(11). PMID: 26234505    Free PMC article.
Scale-up of a physiologically-based pharmacokinetic model to predict the disposition of monoclonal antibodies in monkeys.
Patrick M Glassman, Yang Chen, Joseph P Balthasar.
J Pharmacokinet Pharmacodyn, 2015 Sep 14; 42(5). PMID: 26364301
The EGFR-HER2 module: a stem cell approach to understanding a prime target and driver of solid tumors.
M R Schneider, Y Yarden.
Oncogene, 2015 Oct 06; 35(23). PMID: 26434585    Free PMC article.
Review.
The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways.
Zaklina Kovacevic, Sharleen V Menezes, +4 authors, Des R Richardson.
J Biol Chem, 2015 Nov 05; 291(3). PMID: 26534963    Free PMC article.
HER2 induced EMT and tumorigenicity in breast epithelial progenitor cells is inhibited by coexpression of EGFR.
S Ingthorsson, K Andersen, +3 authors, T Gudjonsson.
Oncogene, 2015 Dec 22; 35(32). PMID: 26686087    Free PMC article.
Activated ErbB3 Translocates to the Nucleus via Clathrin-independent Endocytosis, Which Is Associated with Proliferating Cells.
Raymond Reif, Alshaimaa Adawy, +6 authors, Jan G Hengstler.
J Biol Chem, 2016 Jan 01; 291(8). PMID: 26719328    Free PMC article.
Marked enhancement of lysosomal targeting and efficacy of ErbB2-targeted drug delivery by HSP90 inhibition.
Srikumar M Raja, Swapnil S Desale, +10 authors, Hamid Band.
Oncotarget, 2016 Feb 10; 7(9). PMID: 26859680    Free PMC article.
Role of EGF receptor ligands in TCDD-induced EGFR down-regulation and cellular proliferation.
Christina M Campion, Sandra Leon Carrion, +3 authors, Judith A Cole.
Chem Biol Interact, 2016 Apr 28; 253. PMID: 27117977    Free PMC article.
Physiologically-based pharmacokinetic modeling to predict the clinical pharmacokinetics of monoclonal antibodies.
Patrick M Glassman, Joseph P Balthasar.
J Pharmacokinet Pharmacodyn, 2016 Jul 06; 43(4). PMID: 27377311
Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity.
Gabriella Mincione, Maria Carmela Di Marcantonio, +8 authors, Raffaella Muraro.
Oncotarget, 2016 Nov 02; 7(46). PMID: 27732953    Free PMC article.
The Contribution of Spatial and Temporal Molecular Networks in the Induction of Long-term Memory and Its Underlying Synaptic Plasticity.
Anastasios A Mirisis, Anamaria Alexandrescu, Thomas J Carew, Ashley M Kopec.
AIMS Neurosci, 2016 Nov 08; 3(3). PMID: 27819030    Free PMC article.
ERBB3: A potential serum biomarker for early detection and therapeutic target for devil facial tumour 1 (DFT1).
Dane A Hayes, Dale A Kunde, +3 authors, Elizabeth T Snow.
PLoS One, 2017 Jun 08; 12(6). PMID: 28591206    Free PMC article.
A Novel Signaling Complex between TROY and EGFR Mediates Glioblastoma Cell Invasion.
Zonghui Ding, Alison Roos, +6 authors, Joseph C Loftus.
Mol Cancer Res, 2017 Nov 10; 16(2). PMID: 29117939    Free PMC article.
Emerging functions of the EGFR in cancer.
Sara Sigismund, Daniele Avanzato, Letizia Lanzetti.
Mol Oncol, 2017 Nov 11; 12(1). PMID: 29124875    Free PMC article.
Highly Cited. Review.
Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine.
Yu Muta, Yoshihisa Fujita, +7 authors, Masamichi Imajo.
Nat Commun, 2018 Jun 07; 9(1). PMID: 29872037    Free PMC article.
SORLA regulates endosomal trafficking and oncogenic fitness of HER2.
Mika Pietilä, Pranshu Sahgal, +15 authors, Johanna Ivaska.
Nat Commun, 2019 May 30; 10(1). PMID: 31138794    Free PMC article.
HER2-Targeted PET Imaging and Therapy of Hyaluronan-Masked HER2-Overexpressing Breast Cancer.
Patricia M R Pereira, Ashwin Ragupathi, +3 authors, Jason S Lewis.
Mol Pharm, 2019 Dec 06; 17(1). PMID: 31804840    Free PMC article.
Regulation of the EGFR/ErbB signalling by clathrin in response to various ligands in hepatocellular carcinoma cell lines.
Yuanhui Liu, Claire Calmel, +3 authors, Françoise Praz.
J Cell Mol Med, 2020 Jun 10; 24(14). PMID: 32515546    Free PMC article.
Anti-EGFR therapy in metastatic colorectal cancer: mechanisms and potential regimens of drug resistance.
Qing-Hai Li, Ying-Zhao Wang, +7 authors, Jin-Ning Ye.
Gastroenterol Rep (Oxf), 2020 Jul 16; 8(3). PMID: 32665850    Free PMC article.
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The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer.
Jinrui Zhang, Shuyan Liu, +13 authors, Han Liu.
Cell Death Differ, 2020 Apr 25; 27(9). PMID: 32327714    Free PMC article.
Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer.
Denis M Collins, Neil T Conlon, +4 authors, John Crown.
Cancers (Basel), 2019 May 31; 11(6). PMID: 31141894    Free PMC article.
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Synthesis and Enhanced Cellular Uptake In Vitro of Anti-HER2 Multifunctional Gold Nanoparticles.
Esteban Cruz, Veysel Kayser.
Cancers (Basel), 2019 Jun 27; 11(6). PMID: 31234432    Free PMC article.
Kinetics of receptor tyrosine kinase activation define ERK signaling dynamics.
Anatoly Kiyatkin, Iris K van Alderwerelt van Rosenburgh, Daryl E Klein, Mark A Lemmon.
Sci Signal, 2020 Aug 21; 13(645). PMID: 32817373    Free PMC article.
Coordinated dysregulation of cancer progression by the HER family and p21-activated kinases.
Rakesh Kumar, Aswathy Mary Paul, +2 authors, M Radhakrishna Pillai.
Cancer Metastasis Rev, 2020 Aug 21; 39(3). PMID: 32820388
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Neuregulins in Neurodegenerative Diseases.
Guan-Yong Ou, Wen-Wen Lin, Wei-Jiang Zhao.
Front Aging Neurosci, 2021 Apr 27; 13. PMID: 33897409    Free PMC article.
A Phase I Study of Alpelisib in Combination with Trastuzumab and LJM716 in Patients with PIK3CA-Mutated HER2-Positive Metastatic Breast Cancer.
Komal Jhaveri, Joshua Z Drago, +10 authors, Shanu Modi.
Clin Cancer Res, 2021 May 06; 27(14). PMID: 33947692    Free PMC article.
Nrg1β Released in Remote Ischemic Preconditioning Improves Myocardial Perfusion and Decreases Ischemia/Reperfusion Injury via ErbB2-Mediated Rescue of Endothelial Nitric Oxide Synthase and Abrogation of Trx2 Autophagy.
Venkatesh Kundumani-Sridharan, Jaganathan Subramani, Cade Owens, Kumuda C Das.
Arterioscler Thromb Vasc Biol, 2021 May 28; 41(8). PMID: 34039018    Free PMC article.