Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 20 February 2004:
Vol. 303. no. 5661, pp. 1179 - 1181
DOI: 10.1126/science.1092089
Prev | Table of Contents | Next

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Analysis of PTEN Complex Assembly and Identification of Heterogeneous Nuclear Ribonucleoprotein C as a Component of the PTEN-associated Complex.
S. Mosessian, N. K. Avliyakulov, D. J. Mulholland, P. Boontheung, J. A. Loo, and H. Wu (2009)
J. Biol. Chem. 284, 30159-30166
   Abstract »    Full Text »    PDF »
Phosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes.
D. K. Finlay, L. V. Sinclair, C. Feijoo, C. M. Waugh, T. J. Hagenbeek, H. Spits, and D. A. Cantrell (2009)
J. Exp. Med. 206, 2441-2454
   Abstract »    Full Text »    PDF »
p85 Associates with Unphosphorylated PTEN and the PTEN-Associated Complex.
R. Rabinovsky, P. Pochanard, C. McNear, S. M. Brachmann, J. S. Duke-Cohan, L. A. Garraway, and W. R. Sellers (2009)
Mol. Cell. Biol. 29, 5377-5388
   Abstract »    Full Text »    PDF »
Cell type specificity of PI3K signaling in Pdk1- and Pten-deficient brains.
N. Chalhoub, G. Zhu, X. Zhu, and S. J. Baker (2009)
Genes & Dev. 23, 1619-1624
   Abstract »    Full Text »    PDF »
Loss of Phosphatase and Tensin Homologue Deleted on Chromosome 10 Engages ErbB3 and Insulin-Like Growth Factor-I Receptor Signaling to Promote Antiestrogen Resistance in Breast Cancer.
T. W. Miller, M. Perez-Torres, A. Narasanna, M. Guix, O. Stal, G. Perez-Tenorio, A. M. Gonzalez-Angulo, B. T. Hennessy, G. B. Mills, J. P. Kennedy, et al. (2009)
Cancer Res. 69, 4192-4201
   Abstract »    Full Text »    PDF »
Pten Deletion in Adult Neural Stem/Progenitor Cells Enhances Constitutive Neurogenesis.
C. Gregorian, J. Nakashima, J. Le Belle, J. Ohab, R. Kim, A. Liu, K. B. Smith, M. Groszer, A. D. Garcia, M. V. Sofroniew, et al. (2009)
J. Neurosci. 29, 1874-1886
   Abstract »    Full Text »    PDF »
RhoA-Dependent Regulation of Cell Migration by the Tumor Suppressor hSNF5/INI1.
J. Caramel, F. Quignon, and O. Delattre (2008)
Cancer Res. 68, 6154-6161
   Abstract »    Full Text »    PDF »
The Protein Phosphatase Activity of PTEN Regulates Src Family Kinases and Controls Glioma Migration.
N. Dey, H. E. Crosswell, P. De, R. Parsons, Q. Peng, J. D. Su, and D. L. Durden (2008)
Cancer Res. 68, 1862-1871
   Abstract »    Full Text »    PDF »
New insights into PTEN.
T. Tamguney and D. Stokoe (2007)
J. Cell Sci. 120, 4071-4079
   Abstract »    Full Text »    PDF »
Regulation of PTEN Activity by Its Carboxyl-terminal Autoinhibitory Domain.
L. Odriozola, G. Singh, T. Hoang, and A. M. Chan (2007)
J. Biol. Chem. 282, 23306-23315
   Abstract »    Full Text »    PDF »
Mechanisms of Vascular Smooth Muscle Cell Migration.
W. T. Gerthoffer (2007)
Circ. Res. 100, 607-621
   Abstract »    Full Text »    PDF »
Molecular Pathways Regulating Pro-migratory Effects of Hedgehog Signaling.
E. Hochman, A. Castiel, J. Jacob-Hirsch, N. Amariglio, and S. Izraeli (2006)
J. Biol. Chem. 281, 33860-33870
   Abstract »    Full Text »    PDF »
Nuclear Localization of PTEN by a Ran-dependent Mechanism Enhances Apoptosis: Involvement of an N-Terminal Nuclear Localization Domain and Multiple Nuclear Exclusion Motifs.
A. Gil, A. Andres-Pons, E. Fernandez, M. Valiente, J. Torres, J. Cervera, and R. Pulido (2006)
Mol. Biol. Cell 17, 4002-4013
   Abstract »    Full Text »    PDF »
PTEN Deletion Leads to Up-regulation of a Secreted Growth Factor Pleiotrophin.
G. Li, Y. Hu, Y. Huo, M. Liu, D. Freeman, J. Gao, X. Liu, D.-C. Wu, and H. Wu (2006)
J. Biol. Chem. 281, 10663-10668
   Abstract »    Full Text »    PDF »
Tumor suppressor PTEN acts through dynamic interaction with the plasma membrane..
F. Vazquez, S. Matsuoka, W. R. Sellers, T. Yanagida, M. Ueda, and P. N. Devreotes (2006)
PNAS 103, 3633-3638
   Abstract »    Full Text »    PDF »
PTEN couples Sema3A signalling to growth cone collapse..
N. H. Chadborn, A. I. Ahmed, M. R. Holt, R. Prinjha, G. A. Dunn, G. E. Jones, and B. J. Eickholt (2006)
J. Cell Sci. 119, 951-957
   Abstract »    Full Text »    PDF »
High Frequency of Coexistent Mutations of PIK3CA and PTEN Genes in Endometrial Carcinoma.
K. Oda, D. Stokoe, Y. Taketani, and F. McCormick (2005)
Cancer Res. 65, 10669-10673
   Abstract »    Full Text »    PDF »
TGF{beta}-induced downregulation of E-cadherin-based cell-cell adhesion depends on PI3-kinase and PTEN.
R. Vogelmann, M.-D. Nguyen-tat, K. Giehl, G. Adler, D. Wedlich, and A. Menke (2005)
J. Cell Sci. 118, 4901-4912
   Abstract »    Full Text »    PDF »
Negative regulation of CXCR4-mediated chemotaxis by the lipid phosphatase activity of tumor suppressor PTEN.
P. Gao, R. L. Wange, N. Zhang, J. J. Oppenheim, and O. M. Z. Howard (2005)
Blood 106, 2619-2626
   Abstract »    Full Text »    PDF »
Mutations of Phosphatase and Tensin Homolog Deleted from Chromosome 10 in Canine Hemangiosarcoma.
E. B. Dickerson, R. Thomas, S. P. Fosmire, A. R. Lamerato-Kozicki, S. R. Bianco, J. W. Wojcieszyn, M. Breen, S. C. Helfand, and J. F. Modiano (2005)
Vet. Pathol. 42, 618-632
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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.
A. Xiao, C. Yin, C. Yang, A. Di Cristofano, P. P. Pandolfi, and T. Van Dyke (2005)
Cancer Res. 65, 5172-5180
   Abstract »    Full Text »    PDF »
PIK3CA Mutations Correlate with Hormone Receptors, Node Metastasis, and ERBB2, and Are Mutually Exclusive with PTEN Loss in Human Breast Carcinoma.
L. H. Saal, K. Holm, M. Maurer, L. Memeo, T. Su, X. Wang, J. S. Yu, P.-O. Malmstrom, M. Mansukhani, J. Enoksson, et al. (2005)
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
   Abstract »    Full Text »    PDF »
Phosphatase and tensin homologue growth suppression without phosphatase.
D. Stokoe and J. F. Costello (2005)
PNAS 102, 2677-2678
   Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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.
F. Okahara, H. Ikawa, Y. Kanaho, and T. Maehama (2004)
J. Biol. Chem. 279, 45300-45303
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Glioblastomas on the Move.
A. Merlo and B. Bettler (2004)
Sci. STKE 2004, pe18
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)