HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 11, 9733-9742, March 12, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/11/9733    most recent M311400200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mahabeleshwar, G. H. Articles by Kundu, G. C. Search for Related Content PubMed PubMed Citation Articles by Mahabeleshwar, G. H. Articles by Kundu, G. C. Social Bookmarking                      What's this?

Tyrosine Kinase, p56^lck-induced Cell Motility, and Urokinase-type Plasminogen Activator Secretion Involve Activation of Epidermal Growth Factor Receptor/Extracellular Signal Regulated Kinase Pathways^*

Ganapati H. Mahabeleshwar, Riku Das, and Gopal C. Kundu

From the National Centre for Cell Science (NCCS), NCCS Complex, Pune 411007, India

We have recently reported that tyrosine kinase, p56^lck regulates cell motility and nuclear factor B-mediated secretion of urokinase-type plasminogen activator (uPA) through tyrosine phosphorylation of IB following hypoxia/reoxygenation (Mahabeleshwar, G. H., and Kundu, G. C. (2003) J. Biol. Chem. 278, 52598–52612). However, the role of hypoxia/reoxygenation (H/R) on ERK1/2-mediated uPA secretion and cell motility and the involvement of p56^lck and EGF receptor in these processes in breast cancer cells is not well defined. We provide here evidence that H/R induces Lck kinase activity and Lck-dependent tyrosine phosphorylation of EGF receptor in highly invasive (MDA-MB-231) and low invasive (MCF-7) breast cancer cells. H/R also stimulates MEK-1 and ERK1/2 phosphorylations, and H/R-induced phosphorylations were suppressed by the dominant negative form of Lck (DN Lck, K273R) as well as pharmacological inhibitors of EGF receptor and Lck indicating that EGF receptors and Lck are involved in these processes. Transfection of these cells with wild type Lck or Lck F505 (Y505F) but not with Lck F394 (Y394F) induced phosphorylations of EGF receptor followed by MEK-1 and ERK1/2, suggesting that Lck is upstream of EGF receptor and Tyr-394 of Lck is crucial for these processes. H/R also induced uPA secretion and cell motility in these cells. DN Lck and inhibitors of Lck, EGF receptor, and MEK-1 suppressed H/R-induced uPA secretion and cell motility. To our knowledge, this is the first report that p56^lck in presence of H/R regulates MEK-1-dependent ERK1/2 phosphorylation and uPA secretion through tyrosine phosphorylation of EGF receptor, and it further demonstrates that all of these signaling molecules ultimately control the motility of breast cancer cells.

Received for publication, October 17, 2003 , and in revised form, December 23, 2003.

^* This work was supported by the Council of Scientific and Industrial Research, Government of India (to G. H. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 91-20-25690931 (ext. 203); Fax: 91-20-25692259; E-mail: gopalkundu{at}hotmail.com.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. Du, H. Leung, K.M. F. Khan, C. G. Miller, K. Subbaramaiah, D. J. Falcone, and A. J. Dannenberg Tobacco Smoke Induces Urokinase-Type Plasminogen Activator and Cell Invasiveness: Evidence for an Epidermal Growth Factor Receptor Dependent Mechanism Cancer Res., September 15, 2007; 67(18): 8966 - 8972. [Abstract] [Full Text] [PDF]

				H.-Y. Chen, S.-L. Yu, C.-H. Chen, G.-C. Chang, C.-Y. Chen, A. Yuan, C.-L. Cheng, C.-H. Wang, H.-J. Terng, S.-F. Kao, et al. A Five-Gene Signature and Clinical Outcome in Non-Small-Cell Lung Cancer N. Engl. J. Med., January 4, 2007; 356(1): 11 - 20. [Abstract] [Full Text] [PDF]

				T. Pertel, D. Zhu, R. A. Panettieri, N. Yamaguchi, C. W. Emala, and C. A. Hirshman Expression and muscarinic receptor coupling of Lyn kinase in cultured human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L492 - L500. [Abstract] [Full Text] [PDF]

				S. Banerjee, K. Sengupta, N. K. Saxena, K. Dhar, and S. K. Banerjee Epidermal Growth Factor Induces WISP-2/CCN5 Expression in Estrogen Receptor-{alpha}-Positive Breast Tumor Cells through Multiple Molecular Cross-talks Mol. Cancer Res., March 1, 2005; 3(3): 151 - 162. [Abstract] [Full Text] [PDF]