AJP - GI Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol (July 29, 2004). doi:10.1152/ajpgi.00253.2004
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Movie
Right arrow All Versions of this Article:
287/6/G1227    most recent
00253.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Andl, C. D.
Right arrow Articles by Rustgi, A. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Andl, C. D.
Right arrow Articles by Rustgi, A. K.
Submitted on June 10, 2004
Accepted on July 21, 2004

EGFR induced cell migration is mediated predominantly by the JAK/Stat pathway in primary esophageal keratinocytes

Claudia D. Andl1, Takaaki Mizushima1, Kenji Oyama1, Mark Bowser1, Hiroshi Nakagawa1, and Anil K. Rustgi1*

1 Gastroenterology Division, University of Pennsylvania, Philadelphia, PA, USA; Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA; Abramson Cancer Center and Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA

* To whom correspondence should be addressed. E-mail: anil2{at}mail.med.upenn.edu.

The epidermal growth factor receptor (EGFR) activates several signaling cascades in response to EGF stimulation. One of these signaling events involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat), whereas another involves activation of the phosphatidylinositol 3-OH kinase (PI3K) pathway. Two possibilities for Stat activation exist, a Janus kinase (Jak)-dependent and a Jak-independent mechanism. Herein, we demonstrate that EGFR overexpression in primary esophageal keratinocytes activates Stat in a Jak-dependent fashion with the functional consequence of enhanced cell migration, which can be abolished by use of a Jak-specific inhibitor, AG490. We determined the mechanisms underlying the signal transduction pathway responsible for increased cell migration. Stimulation of EGFR induces Tyr-701 phosphorylation of Stat1 and initiates complex formation of Stat1 and Stat3 with Jak1 and Jak2. Thereafter, the Stats translocate to the nucleus within 15 minutes. In addition, we found that activation of this signaling pathway results in matrix metalloproteinase-1 (MMP-1) activity. By contrast, Akt activation does not impact upon the EGFR/Stats/Jaks complex formation and nuclear translocation of the Stats with subsequent MMP-1 activity, although Akt activation may contribute to cell migration through an independent mechanism. Taken together, we find that the recruitment of the Stat/Jak complex by EGFR is responsible for keratinocyte migration that in turn might be mediated by MMP-1 activation.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
K. L. Wu, H. Miao, and S. Khan
JAK kinases promote invasiveness in VHL-mediated renal cell carcinoma by a suppressor of cytokine signaling-regulated, HIF-independent mechanism
Am J Physiol Renal Physiol, December 1, 2007; 293(6): F1836 - F1846.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
S. Zhuang, Y. Yan, R. A. Daubert, and R. G. Schnellmann
Epiregulin promotes proliferation and migration of renal proximal tubular cells
Am J Physiol Renal Physiol, July 1, 2007; 293(1): F219 - F226.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S.-H. Kim, H. Nakagawa, A. Navaraj, Y. Naomoto, A. J.P. Klein-Szanto, A. K. Rustgi, and W. S. El-Deiry
Tumorigenic Conversion of Primary Human Esophageal Epithelial Cells Using Oncogene Combinations in the Absence of Exogenous Ras
Cancer Res., November 1, 2006; 66(21): 10415 - 10424.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
S. Pankow, C. Bamberger, A. Klippel, and S. Werner
Regulation of epidermal homeostasis and repair by phosphoinositide 3-kinase
J. Cell Sci., October 1, 2006; 119(19): 4033 - 4046.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. J. Holtzman, J. T. Battaile, and A. C. Patel
Immunogenetic Programs for Viral Induction of Mucous Cell Metaplasia
Am. J. Respir. Cell Mol. Biol., July 1, 2006; 35(1): 29 - 39.
[Full Text] [PDF]

Home page
 Mol Cancer ResHome page
S. Y. Eum, Y. W. Lee, B. Hennig, and M. Toborek
Interplay between Epidermal Growth Factor Receptor and Janus Kinase 3 Regulates Polychlorinated Biphenyl-Induced Matrix Metalloproteinase-3 Expression and Transendothelial Migration of Tumor Cells
Mol. Cancer Res., June 1, 2006; 4(6): 361 - 370.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Shida, J. Kitayama, K. Mori, T. Watanabe, and H. Nagawa
Transactivation of Epidermal Growth Factor Receptor Is Involved in Leptin-Induced Activation of Janus-Activated Kinase 2 and Extracellular Signal-Regulated Kinase 1/2 in Human Gastric Cancer Cells
Cancer Res., October 15, 2005; 65(20): 9159 - 9163.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
G.-H. Baeg, R. Zhou, and N. Perrimon
Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila
Genes & Dev., August 15, 2005; 19(16): 1861 - 1870.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.