To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

The kinase ALK stimulates… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

The kinase ALK stimulates the kinase ERK5 to promote the expression of the oncogene MYCN in neuroblastoma

Journal article
Authors Ganesh Umapathy
A. El Wakil
Barbara Witek
L. Chesler
L. Danielson
X. M. Deng
N. S. Gray
M. Johansson
S. Kvarnbrink
K. Ruuth
C. Schonherr
Ruth H. Palmer
Bengt Hallberg
Published in Science Signaling
Volume 7
Issue 349
Pages ra102
ISSN 1945-0877
Publication year 2014
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages ra102
Language en
Links dx.doi.org/10.1126/scisignal.200547...
Keywords ACTIVATED PROTEIN-KINASE, SIGNAL-REGULATED KINASE-5, EPIDERMAL-GROWTH-FACTOR, LARGE-CELL LYMPHOMA, ANAPLASTIC LYMPHOMA, LUNG-CANCER, TYROSINE KINASE, N-MYC, GENE, MUTATIONS, Biochemistry & Molecular Biology, Cell Biology
Subject categories Cell biology, Cell Biology, Biochemistry and Molecular Biology

Abstract

Anaplastic lymphoma kinase (ALK) is an important molecular target in neuroblastoma. Although tyrosine kinase inhibitors abrogating ALK activity are currently in clinical use for the treatment of ALK-positive (ALK(+)) disease, monotherapy with ALK tyrosine kinase inhibitors may not be an adequate solution for ALK(+) neuroblastoma patients. Increased expression of the gene encoding the transcription factor MYCN is common in neuroblastomas and correlates with poor prognosis. We found that the kinase ERK5 [also known as big mitogen-activated protein kinase (MAPK) 1 (BMK1)] is activated by ALK through a pathway mediated by phosphoinositide 3-kinase (PI3K), AKT, MAPK kinase kinase 3 (MEKK3), and MAPK kinase 5 (MEK5). ALK-induced transcription of MYCN and stimulation of cell proliferation required ERK5. Pharmacological or RNA interference-mediated inhibition of ERK5 suppressed the proliferation of neuroblastoma cells in culture and enhanced the antitumor efficacy of the ALK inhibitor crizotinib in both cells and xenograft models. Together, our results indicate that ERK5 mediates ALK-induced transcription of MYCN and proliferation of neuroblastoma, suggesting that targeting both ERK5 and ALK may be beneficial in neuroblastoma patients.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?