Constitutive activation of c-Jun N-terminal kinase by a mutant epidermal growth factor receptor.

The Journal of Biological Chemistry
M A AntonyakA J Wong

Abstract

Epidermal growth factor receptor (EGF) variant type III (EGFRvIII) is a constitutively active, naturally occurring mutation of the EGF receptor that is found in many types of human tumors. When overexpressed in NIH3T3 fibroblasts, EGFRvIII induces transformation by enhancing cell growth and reducing apoptosis. Analysis of downstream signaling pathways has revealed that extracellular signal-regulated kinase activity is down-regulated, raising doubt as to the significance of this pathway in promoting transformation. We investigated whether the c-Jun N-terminal kinase (JNK) pathway was affected by EGFRvIII. NIH3T3 cells expressing EGFRvIII exhibited a high basal level of JNK activity, which was not present in cells overexpressing the normal EGF receptor. Treatment of cells overexpressing EGFRvIII with inhibitors of the EGF receptor or phosphatidylinositol 3-kinase resulted in the down-regulation of JNK activity. Furthermore, the down-regulation of JNK activity was associated with a loss of properties related to transformation, and there was no evidence for JNK activity in the promotion of apoptosis in these cells. These findings implicate constitutive activation of the JNK pathway in transformation by EGFRvIII.

References

Apr 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·A J WongB Vogelstein
Nov 24, 1995·Science·Z XiaM E Greenberg
Nov 24, 1995·The Journal of Biological Chemistry·S BagrodiaR A Cerione
Jul 28, 1995·The Journal of Biological Chemistry·K F ToliasC L Carpenter
Mar 1, 1995·Trends in Biochemical Sciences·E Cano, L C Mahadevan
Jan 2, 1994·International Journal of Cancer. Journal International Du Cancer·J SchlegelM Kiessling
Apr 1, 1993·Current Opinion in Cell Biology·A Hall
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·A B RaitanoC L Sawyers
May 1, 1996·The Biochemical Journal·G M BokochA E Traynor-Kaplan
Oct 1, 1996·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·A J Whitmarsh, R J Davis
Feb 7, 1997·Cell·T Hunter
May 15, 1997·The EMBO Journal·G A RodriguesJ Schlessinger
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·C TournierR J Davis

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Citations

Feb 24, 2001·Brain Tumor Pathology·C T KuanD D Bigner
Feb 22, 2008·Histochemistry and Cell Biology·Kirstine RoepstorffBo van Deurs
Jun 11, 2002·Biochemical and Biophysical Research Communications·Youn Wook ChungIck Young Kim
Mar 21, 2003·Biochemical and Biophysical Research Communications·Yasuyoshi MiyataShigeru Kanda
Mar 22, 2003·Experimental Cell Research·Julie L BoernerNita J Maihle
Jan 28, 2012·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Liang ChengShaobo Zhang
Jun 1, 2004·Nature Medicine·Carlos L Arteaga
Jun 17, 2003·Molecular and Cellular Biology·Marina Holgado-Madruga, Albert J Wong
May 24, 2003·Neurosurgery·Gurpreet S Kapoor, Donald M O'Rourke
Apr 6, 2011·Future Oncology·Liang ChengAntonio Lopez-Beltran
Nov 18, 2011·ISRN Oncology·Annamaria Cimini, Rodolfo Ippoliti
Jun 4, 2013·Immunotherapy·Pasquale De BonisAnnunziato Mangiola
May 8, 2014·Journal of Immunology Research·Linda W XuGordon Li
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·D M O'RourkeM I Greene
Mar 29, 2014·Cellular and Molecular Life Sciences : CMLS·Cristina Zahonero, Pilar Sánchez-Gómez
Jul 16, 2010·Expert Review of Molecular Diagnostics·Andreana L Rivera, Christopher E Pelloski
May 15, 2007·FEBS Letters·Oliver RathThomas Metz
Sep 5, 2008·Expert Review of Vaccines·Gordon Li, Albert J Wong
Mar 24, 2012·Neurosurgery Clinics of North America·Joaquin Q Camara-QuintanaGordon Li
Dec 1, 2009·Neurosurgery Clinics of North America·Gordon LiAlbert J Wong
Oct 29, 2015·Journal of Neuroscience Research·Vimal PandeyPhanithi Prakash Babu
May 27, 2008·Current Problems in Cancer·Andreana L RiveraKen Aldape
Sep 12, 2009·Brain Pathology·Bryan D ChoiJohn H Sampson
Apr 24, 2003·Cancer Science·Isamu OkamotoAlbert J Wong
Apr 22, 2003·International Journal of Cancer. Journal International Du Cancer·Manuela Klingler-HoffmannTony Tiganis
Oct 16, 2012·British Journal of Pharmacology·Y T YeungL Munoz

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