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Science 20 February 2004:
Vol. 303. no. 5661, pp. 1179 - 1181
DOI: 10.1126/science.1092089
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Reports

Regulation of Cell Migration by the C2 Domain of the Tumor Suppressor PTEN

Myrto Raftopoulou, Sandrine Etienne-Manneville, Annette Self, Sarah Nicholls, Alan Hall*

PTEN is a tumor suppressor protein that dephosphorylates phosphatidylinositol 3,4,5 trisphosphate and antagonizes the phosphatidylinositol-3 kinase signaling pathway. We show here that PTEN can also inhibit cell migration through its C2 domain, independent of its lipid phosphatase activity. This activity depends on the protein phosphatase activity of PTEN and on dephosphorylation at a single residue, threonine383. The ability of PTEN to control cell migration through its C2 domain is likely to be an important feature of its tumor suppressor activity.

Medical Research Council Laboratory for Molecular Cell Biology and Cell Biology Unit, Cancer Research UK Oncogene and Signal Transduction Group, and Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.

* To whom correspondence should be addressed. E-mail: alan.hall{at}ucl.ac.uk

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M. Valiente, A. Andres-Pons, B. Gomar, J. Torres, A. Gil, C. Tapparel, S. E. Antonarakis, and R. Pulido (2005)
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PTEN deletion in Bergmann glia leads to premature differentiation and affects laminar organization.
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Cancer Res. 65, 5172-5180
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Cancer Res. 65, 2554-2559
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D. Stokoe and J. F. Costello (2005)
PNAS 102, 2677-2678
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From the Cover: Cellular transformation by the MSP58 oncogene is inhibited by its physical interaction with the PTEN tumor suppressor.
K. Okumura, M. Zhao, R. A. DePinho, F. B. Furnari, and W. K. Cavenee (2005)
PNAS 102, 2703-2706
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Vinculin Controls PTEN Protein Level by Maintaining the Interaction of the Adherens Junction Protein {beta}-Catenin with the Scaffolding Protein MAGI-2.
M. C. Subauste, P. Nalbant, E. D. Adamson, and K. M. Hahn (2005)
J. Biol. Chem. 280, 5676-5681
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Prostaglandin E2 Inhibits Fibroblast Migration by E-Prostanoid 2 Receptor-Mediated Increase in PTEN Activity.
E. S. White, R. G. Atrasz, E. G. Dickie, D. M. Aronoff, V. Stambolic, T. W. Mak, B. B. Moore, and M. Peters-Golden (2005)
Am. J. Respir. Cell Mol. Biol. 32, 135-141
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PTEN regulates motility but not directionality during leukocyte chemotaxis.
R. A. Lacalle, C. Gomez-Mouton, D. F. Barber, S. Jimenez-Baranda, E. Mira, C. Martinez-A., A. C. Carrera, and S. Manes (2004)
J. Cell Sci. 117, 6207-6215
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Pten Loss Causes Hypertrophy and Increased Proliferation of Astrocytes In vivo.
M. M. Fraser, X. Zhu, C.-H. Kwon, E. J. Uhlmann, D. H. Gutmann, and S. J. Baker (2004)
Cancer Res. 64, 7773-7779
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Regulation of PTEN Phosphorylation and Stability by a Tumor Suppressor Candidate Protein.
F. Okahara, H. Ikawa, Y. Kanaho, and T. Maehama (2004)
J. Biol. Chem. 279, 45300-45303
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Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation.
G. Mouneimne, L. Soon, V. DesMarais, M. Sidani, X. Song, S.-C. Yip, M. Ghosh, R. Eddy, J. M. Backer, and J. Condeelis (2004)
J. Cell Biol. 166, 697-708
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Glioblastomas on the Move.
A. Merlo and B. Bettler (2004)
Sci. STKE 2004, pe18
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Science. ISSN 0036-8075 (print), 1095-9203 (online)