JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M010847200 on January 31, 2001

J. Biol. Chem., Vol. 276, Issue 18, 15537-15546, May 4, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/18/15537    most recent
M010847200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Barry, O. P.
Right arrow Articles by O'Sullivan, G. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Barry, O. P.
Right arrow Articles by O'Sullivan, G. C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Constitutive ERK1/2 Activation in Esophagogastric Rib Bone Marrow Micrometastatic Cells Is MEK-independent*

Orla P. BarryDagger , Brian Mullan§, Dyane Sheehan, Marcelo G. Kazanietz||, Fergus Shanahan§, J. Kevin Collins, and Gerald C. O'SullivanDagger **

From the Dagger  Cork Cancer Research Center and Departments of § Medicine and  Microbiology, National University of Ireland, Cork, Ireland and the || Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160

In this study, we examined the mitogen-activated protein kinase (MAPK) cascade in micrometastatic cell lines generated from rib bone marrow (RBM) of patients undergoing resection of esophagogastric malignancies. The molecular mechanism(s) involved in esophagogastric MAPK activation have not previously been investigated. Constitutive activation of both ERK1 and -2 isoforms was evident in each of the five RBM cell lines. Elk-1, a transcription factor activated by the ERK1/2 pathway was also found to be constitutively activated. Cell lines generated from metastases of involved lymph nodes (OC2) and ascites (OC1) of patients with esophageal cancer do not display, however, hyperphosphorylation of ERK1/2. Constitutive RBM ERK1/2 activation is protein kinase C and phosphatidylinositol 3-kinase dependent. Surprisingly, constitutive ERK1/2 activation is MEK-independent. Pharmacological inhibition of MEK with two specific inhibitors, PD 98059 and U0126, were both ineffective in blocking ERK activation. Similarly, the use of a dominant negative MEK mutant was without effect. Interestingly, experiments overexpressing two different dominant negative Pak1 mutants significantly reduced RBM ERK1/2 activation, albeit not to the same extent for all cell lines. We also examined the role of three different phosphatases, PAC1, MKP-1, and -2. While RBM ERK1/2 activation was found to be PAC1- and MKP-2-independent, surprisingly, MKP-1 was down-regulated in all five RBM cell lines. In conclusion, we provide evidence for the first time for a MEK-independent constitutive ERK1/2 activation pathway in esophagogastric RBM cell lines. These findings have important implications for drug treatment strategies which currently target MEK in other forms of cancer.

* This work was supported in part by the Irish Cancer Society and a Higher Education Authority Grant.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

** To whom correspondence and reprints should be addressed: Cork Cancer Research Center, Mercy Hospital, Cork, Ireland. Tel.: 21-4271971 (ext. 5397); Fax: 21-4345300; E-mail: geraldc@iol.ie.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Cancer Res.Home page
D. F. Calvisi, F. Pinna, F. Meloni, S. Ladu, R. Pellegrino, M. Sini, L. Daino, M. M. Simile, M. R. De Miglio, P. Virdis, et al.
Dual-Specificity Phosphatase 1 Ubiquitination in Extracellular Signal-Regulated Kinase-Mediated Control of Growth in Human Hepatocellular Carcinoma
Cancer Res., June 1, 2008; 68(11): 4192 - 4200.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Ito, T. Suganami, Y. Miyamoto, Y. Yoshimasa, M. Takeya, Y. Kamei, and Y. Ogawa
Role of MAPK Phosphatase-1 in the Induction of Monocyte Chemoattractant Protein-1 during the Course of Adipocyte Hypertrophy
J. Biol. Chem., August 31, 2007; 282(35): 25445 - 25452.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
C. T. Charalambous, A. Hannigan, P. Tsimbouri, G. M. McPhee, and J. B. Wilson
Latent membrane protein 1-induced EGFR signalling is negatively regulated by TGF{alpha} prior to neoplasia
Carcinogenesis, August 1, 2007; 28(8): 1839 - 1848.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. Ambrose, A. Ryan, G. C. O'Sullivan, C. Dunne, and O. P. Barry
Induction of Apoptosis in Renal Cell Carcinoma by Reactive Oxygen Species: Involvement of Extracellular Signal-Regulated Kinase 1/2, p38{delta}/{gamma}, Cyclooxygenase-2 Down-Regulation, and Translocation of Apoptosis-Inducing Factor
Mol. Pharmacol., June 1, 2006; 69(6): 1879 - 1890.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. P. Duggan, W. M. Gallagher, E. J.P. Fox, M. M. Abdel-Latif, J. V. Reynolds, and D. Kelleher
Low pH induces co-ordinate regulation of gene expression in oesophageal cells
Carcinogenesis, February 1, 2006; 27(2): 319 - 327.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y.-W. Lin and J.-L. Yang
Cooperation of ERK and SCFSkp2 for MKP-1 Destruction Provides a Positive Feedback Regulation of Proliferating Signaling
J. Biol. Chem., January 13, 2006; 281(2): 915 - 926.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Haruki, K. S. Kawaguchi, S. Eichenberger, P. P. Massion, S. Olson, A. Gonzalez, D. P. Carbone, and T. P. Dang
Dominant-Negative Notch3 Receptor Inhibits Mitogen-Activated Protein Kinase Pathway and the Growth of Human Lung Cancers
Cancer Res., May 1, 2005; 65(9): 3555 - 3561.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
R. Steinmetz, H. A. Wagoner, P. Zeng, J. R. Hammond, T. S. Hannon, J. L. Meyers, and O. H. Pescovitz
Mechanisms Regulating the Constitutive Activation of the Extracellular Signal-Regulated Kinase (ERK) Signaling Pathway in Ovarian Cancer and the Effect of Ribonucleic Acid Interference for ERK1/2 on Cancer Cell Proliferation
Mol. Endocrinol., October 1, 2004; 18(10): 2570 - 2582.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Saito, S. Okada, K. Ohshima, E. Yamada, M. Sato, Y. Uehara, H. Shimizu, J. E. Pessin, and M. Mori
Differential Activation of Epidermal Growth Factor (EGF) Receptor Downstream Signaling Pathways by Betacellulin and EGF
Endocrinology, September 1, 2004; 145(9): 4232 - 4243.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y.-W. Lin, S.-M. Chuang, and J.-L. Yang
ERK1/2 Achieves Sustained Activation by Stimulating MAPK Phosphatase-1 Degradation via the Ubiquitin-Proteasome Pathway
J. Biol. Chem., June 6, 2003; 278(24): 21534 - 21541.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
D. A. Buckley, A. Cheng, P. A. Kiely, M. L. Tremblay, and R. O'Connor
Regulation of Insulin-Like Growth Factor Type I (IGF-I) Receptor Kinase Activity by Protein Tyrosine Phosphatase 1B (PTP-1B) and Enhanced IGF-I-Mediated Suppression of Apoptosis and Motility in PTP-1B-Deficient Fibroblasts
Mol. Cell. Biol., April 1, 2002; 22(7): 1998 - 2010.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.