JBC Anatrace, Inc.

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


     

Originally published In Press as doi:10.1074/jbc.M208905200 on December 10, 2002

J. Biol. Chem., Vol. 278, Issue 8, 6209-6221, February 21, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
278/8/6209    most recent
M208905200v1
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 Mahabeleshwar, G. H.
Right arrow Articles by Kundu, G. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mahabeleshwar, G. H.
Right arrow Articles by Kundu, 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?

Syk, a Protein-tyrosine Kinase, Suppresses the Cell Motility and Nuclear Factor kappa B-mediated Secretion of Urokinase Type Plasminogen Activator by Inhibiting the Phosphatidylinositol 3'-Kinase Activity in Breast Cancer Cells*

Ganapati H. Mahabeleshwar and Gopal C. KunduDagger

From the National Centre for Cell Science (NCCS), NCCS Complex, Pune 411 007, India

Tumor growth and metastasis are multifaceted processes that mainly involve cell adhesion, proteolytic degradation of the extracellular matrix, and cell migration. Syk is a member of a tyrosine kinase family that is expressed mostly in hematopoietic cells. Syk is expressed in cell lines of epithelial origin, but its function in these cells remains unknown. Here we report that Syk is expressed in MCF-7 cells but not in MDA-MB-231 cells. The overexpression of wild type Syk kinase but not kinase-negative Syk suppressed cell motility and inhibited the activation of phosphatidylinositol (PI) 3'-kinase in MDA-MB-231 cells. In contrast, when Syk-specific antisense S-oligonucleotide but not the sense S-oligonucleotide was transfected to MCF-7 cells the level of PI 3'-kinase activity as well as cell motility were increased. The MDA-MB-231 cells transfected with wild type Syk cDNA followed by treatment with piceatannol, a Syk inhibitor, enhanced cell motility and PI 3'-kinase activity. Pervanadate, a phosphotyrosine phosphatase inhibitor, induced PI 3'-kinase activity and stimulated the interaction between the inhibitor of nuclear factor kappa Balpha (Ikappa Balpha ) and the p85alpha domain of PI 3'-kinase through tyrosine phosphorylation of the Ikappa Balpha , which ultimately resulted in nuclear factor kappa B (NFkappa B) activation. Pervanadate had no effect on the activation of Syk in these cells. However, Syk suppressed the NFkappa B transcriptional activation and interaction between Ikappa Balpha and PI 3'-kinase by inhibiting the tyrosine phosphorylation of Ikappa Balpha . Syk, PI 3'-kinase inhibitors, and NFkappa B inhibitory peptide inhibited urokinase type plasminogen activator (uPA) secretion and cell motility in these cells. To our knowledge, this is the first report that Syk suppresses the cell motility and inhibits the PI 3'-kinase activity and uPA secretion by blocking NFkappa B activity through tyrosine phosphorylation of Ikappa Balpha . These data further demonstrate a functional molecular link between Syk-regulated PI 3'-kinase activity and NFkappa B-mediated uPA secretion, and all of these ultimately control the motility of breast cancer cells.

* This work was supported by funds from the Department of Biotechnology (to the National Center for Cell Science) and by an extramural fund from the Department of Biotechnology of the government of India (to G. C. K.).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.

Dagger To whom correspondence should be addressed. Tel.: 91-20-569-0931 (ext. 203); Fax: 91-20-569-2259; E-mail: gopalkundu@hotmail.com.

Copyright © 2003 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
 J. Cell Sci.Home page
M. Waldeck-Weiermair, C. Zoratti, K. Osibow, N. Balenga, E. Goessnitzer, M. Waldhoer, R. Malli, and W. F. Graier
Integrin clustering enables anandamide-induced Ca2+ signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression
J. Cell Sci., May 15, 2008; 121(10): 1704 - 1717.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Luangdilok, C. Box, L. Patterson, W. Court, K. Harrington, L. Pitkin, P. Rhys-Evans, P. O-charoenrat, and S. Eccles
Syk Tyrosine Kinase Is Linked to Cell Motility and Progression in Squamous Cell Carcinomas of the Head and Neck
Cancer Res., August 15, 2007; 67(16): 7907 - 7916.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
C.-K. Lee, H. M. Lee, H. J. Kim, H.-J. Park, K.-J. Won, H. Y. Roh, W. S. Choi, B. H. Jeon, T.-K. Park, and B. Kim
Syk contributes to PDGF-BB-mediated migration of rat aortic smooth muscle cells via MAPK pathways
Cardiovasc Res, April 1, 2007; 74(1): 159 - 168.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
Y. Yuan, J. Wang, J. Li, L. Wang, M. Li, Z. Yang, C. Zhang, and J. L. Dai
Frequent Epigenetic Inactivation of Spleen Tyrosine Kinase Gene in Human Hepatocellular Carcinoma.
Clin. Cancer Res., November 15, 2006; 12(22): 6687 - 6695.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. Chakraborty, H. Rangaswami, S. Jain, and G. C. Kundu
Hypoxia Regulates Cross-talk between Syk and Lck Leading to Breast Cancer Progression and Angiogenesis
J. Biol. Chem., April 21, 2006; 281(16): 11322 - 11331.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Zyss, P. Montcourrier, B. Vidal, C. Anguille, F. Merezegue, A. Sahuquet, P. H. Mangeat, and P. J. Coopman
The Syk Tyrosine Kinase Localizes to the Centrosomes and Negatively Affects Mitotic Progression
Cancer Res., December 1, 2005; 65(23): 10872 - 10880.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Wang, E. Devarajan, J. He, S. P. Reddy, and J. L. Dai
Transcription Repressor Activity of Spleen Tyrosine Kinase Mediates Breast Tumor Suppression
Cancer Res., November 15, 2005; 65(22): 10289 - 10297.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Ulanova, L. Puttagunta, M. Marcet-Palacios, M. Duszyk, U. Steinhoff, F. Duta, M.-K. Kim, Z. K. Indik, A. D. Schreiber, and A. D. Befus
Syk tyrosine kinase participates in {beta}1-integrin signaling and inflammatory responses in airway epithelial cells
Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L497 - L507.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Moroni, V. Soldatenkov, L. Zhang, Y. Zhang, G. Stoica, E. Gehan, B. Rashidi, B. Singh, M. Ozdemirli, and S. C. Mueller
Progressive Loss of Syk and Abnormal Proliferation in Breast Cancer Cells
Cancer Res., October 15, 2004; 64(20): 7346 - 7354.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Rangaswami, A. Bulbule, and G. C. Kundu
Nuclear Factor-inducing Kinase Plays a Crucial Role in Osteopontin-induced MAPK/I{kappa}B{alpha} Kinase-dependent Nuclear Factor {kappa}B-mediated Promatrix Metalloproteinase-9 Activation
J. Biol. Chem., September 10, 2004; 279(37): 38921 - 38935.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M.-T. Lin, C.-C. Chang, S.-T. Chen, H.-L. Chang, J.-L. Su, Y.-P. Chau, and M.-L. Kuo
Cyr61 Expression Confers Resistance to Apoptosis in Breast Cancer MCF-7 Cells by a Mechanism of NF-{kappa}B-dependent XIAP Up-Regulation
J. Biol. Chem., June 4, 2004; 279(23): 24015 - 24023.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Das, G. H. Mahabeleshwar, and G. C. Kundu
Osteopontin Induces AP-1-mediated Secretion of Urokinase-type Plasminogen Activator through c-Src-dependent Epidermal Growth Factor Receptor Transactivation in Breast Cancer Cells
J. Biol. Chem., March 19, 2004; 279(12): 11051 - 11064.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. H. Mahabeleshwar, R. Das, and G. C. Kundu
Tyrosine Kinase, p56lck-induced Cell Motility, and Urokinase-type Plasminogen Activator Secretion Involve Activation of Epidermal Growth Factor Receptor/Extracellular Signal Regulated Kinase Pathways
J. Biol. Chem., March 12, 2004; 279(11): 9733 - 9742.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Zhong, C.-H. Wu, W.-H. Lee, and C.-P. Liu
{zeta}-Associated Protein of 70 kDa (ZAP-70), but Not Syk, Tyrosine Kinase Can Mediate Apoptosis of T Cells through the Fas/Fas Ligand, Caspase-8 and Caspase-3 Pathways
J. Immunol., February 1, 2004; 172(3): 1472 - 1482.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. H. Mahabeleshwar and G. C. Kundu
Tyrosine Kinase p56lck Regulates Cell Motility and Nuclear Factor {kappa}B-mediated Secretion of Urokinase Type Plasminogen Activator through Tyrosine Phosphorylation of I{kappa}B{alpha} following Hypoxia/Reoxygenation
J. Biol. Chem., December 26, 2003; 278(52): 52598 - 52612.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Das, G. H. Mahabeleshwar, and G. C. Kundu
Osteopontin Stimulates Cell Motility and Nuclear Factor {kappa}B-mediated Secretion of Urokinase Type Plasminogen Activator through Phosphatidylinositol 3-Kinase/Akt Signaling Pathways in Breast Cancer Cells
J. Biol. Chem., August 1, 2003; 278(31): 28593 - 28606.
[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 © 2003 by the American Society for Biochemistry and Molecular Biology.