The oncogenic ErbB-2/ErbB-3 heterodimer is a surrogate receptor of the epidermal growth factor and betacellulin

Oncogene
R Pinkas-KramarskiY Yarden

Abstract

The ErbB-1 receptor tyrosine kinase binds to six different growth factors, whose prototype is the epidermal growth factor (EGF). Two homologous epithelial receptors, ErbB-3 and ErbB-4, bind all isoforms of another family of growth factors, the Neu differentiation factors (NDFs/neuregulins). The fourth member of the ErbB family, ErbB-2, acts as the preferred heterodimeric partner of ligand-occupied complexes of the three other ErbB proteins. Here we report that at high concentrations, EGF can induce cell growth and differentiation in the absence of ErbB-1. This function is shared by betacellulin, but not by three other ligands, including the transforming growth factor alpha (TGFalpha). The functional receptor was identified as a heterodimer between ErbB-3 and ErbB-2, a previously identified oncogenic complex. When singly expressed, neither ErbB-3 nor ErbB-2 can mediate signaling by EGF. In addition, when co-expressed, blocking either receptor by using site-specific antibodies inhibited EGF and betacellulin activities, indicating strict cooperativity between ErbB-3 and ErbB-2. Through analysis of chimeras between EGF and TGFalpha, we identified the middle portion of EGF (loop B) as the site that enables activation of ErbB-2/ErbB-...Continue Reading

Citations

Dec 19, 1998·Microscopy Research and Technique·L G Hudson, L J McCawley
Feb 19, 2010·Cell and Tissue Research·Damian C GenetosMartin A Vidal
Dec 21, 2000·Current Oncology Reports·S SundaresanM X Sliwkowski
Mar 22, 2003·Experimental Cell Research·Ami CitriYosef Yarden
May 29, 2002·Biochimica Et Biophysica Acta·Jemma LawsonAndrew J Dunbar
Jun 12, 2001·Current Opinion in Neurobiology·A Buonanno, G D Fischbach
Aug 15, 2000·The International Journal of Biochemistry & Cell Biology·A J Dunbar, C Goddard
Apr 12, 2008·Cancer Gene Therapy·G Sithanandam, L M Anderson
May 31, 2011·The Journal of Biological Chemistry·Steven M JayLinda G Griffith
Nov 19, 2013·Clinical & Experimental Metastasis·Sandy R LarsonColm Morrissey
Jan 21, 2014·Seminars in Cell & Developmental Biology·Maik DahlhoffMarlon R Schneider
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·L N KlapperY Yarden
Apr 24, 1999·FEBS Letters·J T JonesM X Sliwkowski
Jul 1, 2004·FEBS Letters·Mitchell B BergerMark A Lemmon
Oct 19, 2010·Critical Reviews in Oncology/hematology·Anna EmdeUNKNOWN Association of Radiotherapy and Oncology of the Mediterranean arEa (AROME)
Dec 30, 2014·Journal of Mammary Gland Biology and Neoplasia·A DittrichA Tyson-Capper
May 15, 2012·Biochimica Et Biophysica Acta·Maik DahlhoffMarlon R Schneider
Dec 30, 2009·Gastroenterology·Maik DahlhoffMarlon R Schneider
Jan 16, 2013·Chemotherapy Research and Practice·Zahi MitriRuth O'Regan
Feb 2, 2012·Chemotherapy Research and Practice·Toru Mukohara
Sep 5, 2017·Nanomedicine·Xiaomeng TangJames H Adair
Oct 19, 2001·Oncogene·A Y TsygankovG Swaminathan
Feb 26, 2003·Radiation Research·Paul DentRupert Schmidt-Ullrich
Feb 26, 2009·American Journal of Physiology. Endocrinology and Metabolism·Jasmine V Abella, Morag Park

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