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Science 303 (5661): 1179-1181

Copyright © 2004 by the American Association for the Advancement of Science

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

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

Abstract: 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}

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J. Cell Sci. 119, 951-957
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K. Oda, D. Stokoe, Y. Taketani, and F. McCormick (2005)
Cancer Res. 65, 10669-10673
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   Abstract »    Full Text »    PDF »
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Blood 106, 2619-2626
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Different splicing defects lead to differential effects downstream of the lipid and protein phosphatase activities of PTEN.
S. Agrawal, R. Pilarski, and C. Eng (2005)
Hum. Mol. Genet. 14, 2459-2468
   Abstract »    Full Text »    PDF »
Binding of PTEN to Specific PDZ Domains Contributes to PTEN Protein Stability and Phosphorylation by Microtubule-associated Serine/Threonine Kinases.
M. Valiente, A. Andres-Pons, B. Gomar, J. Torres, A. Gil, C. Tapparel, S. E. Antonarakis, and R. Pulido (2005)
J. Biol. Chem. 280, 28936-28943
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LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes.
H. Mehenni, N. Lin-Marq, K. Buchet-Poyau, A. Reymond, M. A. Collart, D. Picard, and S. E. Antonarakis (2005)
Hum. Mol. Genet. 14, 2209-2219
   Abstract »    Full Text »    PDF »
Nuclear PTEN-Mediated Growth Suppression Is Independent of Akt Down-Regulation.
J.-L. Liu, X. Sheng, Z. K. Hortobagyi, Z. Mao, G. E. Gallick, and W. K. A. Yung (2005)
Mol. Cell. Biol. 25, 6211-6224
   Abstract »    Full Text »    PDF »
PTEN deletion in Bergmann glia leads to premature differentiation and affects laminar organization.
Q. Yue, M. Groszer, J. S. Gil, A. J. Berk, A. Messing, H. Wu, and X. Liu (2005)
Development 132, 3281-3291
   Abstract »    Full Text »    PDF »
Somatic Induction of Pten Loss in a Preclinical Astrocytoma Model Reveals Major Roles in Disease Progression and Avenues for Target Discovery and Validation.
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Cancer Res. 65, 5172-5180
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PIK3CA Mutations Correlate with Hormone Receptors, Node Metastasis, and ERBB2, and Are Mutually Exclusive with PTEN Loss in Human Breast Carcinoma.
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Cancer Res. 65, 2554-2559
   Abstract »    Full Text »    PDF »
PTEN as an effector in the signaling of antimigratory G protein-coupled receptor.
T. Sanchez, S. Thangada, M.-T. Wu, C. D. Kontos, D. Wu, H. Wu, and T. Hla (2005)
PNAS 102, 4312-4317
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Phosphatase and tensin homologue growth suppression without phosphatase.
D. Stokoe and J. F. Costello (2005)
PNAS 102, 2677-2678
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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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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
   Abstract »    Full Text »    PDF »
Regulation of PTEN Phosphorylation and Stability by a Tumor Suppressor Candidate Protein.
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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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