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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2619-2626. Prepublished online as a Blood First Edition Paper on June 30, 2005; DOI 10.1182/blood-2004-08-3362. This Article Full Text (PDF) All Versions of this Article: 2004-08-3362v1 106/8/2619    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gao, P. Articles by Howard, O. M. Z. Search for Related Content PubMed PubMed Citation Articles by Gao, P. Articles by Howard, O. M. Z. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 30, 2004 Accepted June 15, 2005 Negative regulation of CXCR4-mediated chemotaxis by the lipid phosphatase activity of tumor suppressor PTEN Ping Gao, Ronald L Wange, Ning Zhang, Joost J Oppenheim, and O. M. Zack Howard* Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick,National Institutes of Health, Frederick, MD, USA Laboratory of Cellular and Molecular Biology, National Institute of Aging, National Institutes of Health, Baltimore, MD, USA * Corresponding author; email: howardz{at}mail.ncifcrf.gov. PTEN, a multifunctional tumor suppressor, has been shown to play a regulatory role in cell migration. D. discoideum cells lacking PTEN exhibited impaired migration towards chemoattractant gradients. In the present study, we investigated the involvement of PTEN in chemotaxis of mammalian cells by examining PTEN-null Jurkat T cells. We observed that, in contrast to observations made in D. discoideum, PTEN-null Jurkat T cells exhibited potent chemotactic responses to the chemokine, SDF-1,indicating that PTEN was not requisite for CXCR4-mediated chemotaxis of Jurkat cells. Conversely, reconstitution of PTEN in Jurkat cells by using a Tet-on inducible expression system down-regulated CXCR4-mediated chemotaxis. Furthermore, we established the lipid phosphatase activity of PTEN as essential for its inhibitory effect on chemotaxis. In addition, using PTEN-expressing T cell lines and primary T cells; we demonstrated that down-regulation of PTEN expression with vector-based siRNAs enhanced CXCR4-mediated chemotaxis. Based on these results, we conclude that PTEN expression negatively regulates chemotaxis of lymphoid mammalian cells via its lipid phosphatase activity. Our findings may account for the reported increase in metastatic activity of PTEN-null tumor cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Sarraj, S. Massberg, Y. Li, A. Kasorn, K. Subramanian, F. Loison, L. E. Silberstein, U. von Andrian, and H. R. Luo Myeloid-Specific Deletion of Tumor Suppressor PTEN Augments Neutrophil Transendothelial Migration during Inflammation J. Immunol., June 1, 2009; 182(11): 7190 - 7200. [Abstract] [Full Text] [PDF] K. Sakamoto, K. Iwasaki, H. Sugiyama, and Y. Tsuji Role of the Tumor Suppressor PTEN in Antioxidant Responsive Element-mediated Transcription and Associated Histone Modifications Mol. Biol. Cell, March 15, 2009; 20(6): 1606 - 1617. [Abstract] [Full Text] [PDF] T. Landemaine, A. Jackson, A. Bellahcene, N. Rucci, S. Sin, B. M. Abad, A. Sierra, A. Boudinet, J.-M. Guinebretiere, E. Ricevuto, et al. A Six-Gene Signature Predicting Breast Cancer Lung Metastasis Cancer Res., August 1, 2008; 68(15): 6092 - 6099. [Abstract] [Full Text] [PDF] S. J. Harris, R. V. Parry, J. Westwick, and S. G. Ward Phosphoinositide Lipid Phosphatases: Natural Regulators of Phosphoinositide 3-Kinase Signaling in T Lymphocytes J. Biol. Chem., February 1, 2008; 283(5): 2465 - 2469. [Abstract] [Full Text] [PDF] S. Basu, N. T. Ray, S. J. Atkinson, and H. E. Broxmeyer Protein Phosphatase 2A Plays an Important Role in Stromal Cell-Derived Factor-1/CXC Chemokine Ligand 12-Mediated Migration and Adhesion of CD34+ Cells J. Immunol., September 1, 2007; 179(5): 3075 - 3085. [Abstract] [Full Text] [PDF] Z Wu, K. McRoberts, and D Theodorescu The role of PTEN in prostate cancer cell tropism to the bone micro-environment Carcinogenesis, July 1, 2007; 28(7): 1393 - 1400. [Abstract] [Full Text] [PDF] K. K. Subramanian, Y. Jia, D. Zhu, B. T. Simms, H. Jo, H. Hattori, J. You, J. P. Mizgerd, and H. R. Luo Tumor suppressor PTEN is a physiologic suppressor of chemoattractant-mediated neutrophil functions Blood, May 1, 2007; 109(9): 4028 - 4037. [Abstract] [Full Text] [PDF]

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