PMID: 11341977May 9, 2001Paper

Activation of extracellular-regulated kinases by normal and mutant EGF receptors

Biochimica Et Biophysica Acta
I A Lorimer, S J Lavictoire

Abstract

Glioblastoma cells express a mutant EGF receptor (EGFRvIII) that has constitutive tyrosine kinase activity and enhances their tumorigenicity. Here we show that EGFRvIII promotes constitutive phosphorylation of extracellular regulated kinases (ERKs) in glioblastoma cells in the absence of EGF. EGFRvIII also promoted constitutive activation of phosphoinositide 3-kinase in these cells, as assessed by phosphorylation of protein kinase B/akt. As expected, phosphorylation of protein kinase B/akt was blocked by the phosphoinositide 3-kinase inhibitors wortmannin and LY294002. Less expectedly, we found that this treatment also blocked EGFRvIII-induced phosphorylation of ERKs. In contrast, ERK phosphorylation induced by EGF-activated normal EGF receptor in the same cells was largely unaffected by treatment with phosphoinositide 3-kinase inhibitors. This difference in behavior between the normal receptor and EGFRvIII was not due to differences in the levels of activated EGFRvIII and wild-type EGF receptor, as the two types of receptor were tyrosine phosphorylated to a similar extent under the experimental conditions used. EGFRvIII activation of ERKs was also sensitive to the phospholipase C inhibitor U73122, whereas ERK activation by nor...Continue Reading

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Citations

Aug 7, 2008·Neuro-oncology·Claire Marie-Elisabeth SauvageotPatrick Yung Chih Wen
Mar 28, 2009·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Hui K GanRodney B Luwor
Feb 6, 2003·International Journal of Cancer. Journal International Du Cancer·Maria WartenbergHeinrich Sauer
Feb 10, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jörn M SchattenbergMark J Czaja
Oct 22, 2008·Expert Review of Neurotherapeutics·Hari R KumarLinda H Malkas
Dec 30, 2003·International Journal of Cancer. Journal International Du Cancer·Mikkel W PedersenHans S Poulsen
Sep 20, 2006·Expert Opinion on Therapeutic Targets·Kenneth L van Golen
Jun 21, 2017·International Journal of Molecular Sciences·Stefanie Keller, Mirko H H Schmidt
Jun 11, 2002·American Journal of Physiology. Cell Physiology·J E DumontC Maenhaut
Dec 10, 2002·The Journal of Biological Chemistry·Sylvie J LavictoireIan A J Lorimer
May 22, 2016·Molecular and Cellular Biochemistry·Sanchita RauthNabendu Murmu
Jun 11, 2002·American Journal of Physiology. Cell Physiology·Tim R BilderbackKarin D Rodland
Jul 19, 2008·Bioscience Reports·Jose P Palma-NicolasAna María López-Colomé
Aug 19, 2015·Cancer Research·Gao GuoAmyn A Habib
Dec 18, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Evan K DayMatthew J Lazzara

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