Regulation of cell migration by the C2 domain of the tumor suppressor PTEN

被引：269

作者：

Raftopoulou, M

Etienne-Manneville, S

Self, A

Nicholls, S

Hall, A

机构：

[1] UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England

[2] UCL, Cell Biol Unit, Canc Res UK Oncogene & Signal Transduct Grp, London WC1E 6BT, England

[3] UCL, Dept Biochem & Mol Biol, London WC1E 6BT, England

来源：

SCIENCE | 2004年 / 303卷 / 5661期

关键词：

D O I：

10.1126/science.1092089

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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, threonine(383). The ability of PTEN to control cell migration through its C2 domain is likely to be an important feature of its tumor suppressor activity.

引用

收藏

页码：1179 / 1181

页数：3

相关论文

共 22 条

[11] PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer [J].

Li, J ;

Yen, C ;

Liaw, D ;

Podsypanina, K ;

Bose, S ;

Wang, SI ;

Puc, J ;

Miliaresis, C ;

Rodgers, L ;

McCombie, R ;

Bigner, SH ;

Giovanella, BC ;

Ittmann, M ;

Tycko, B ;

Hibshoosh, H ;

Wigler, MH ;

Parsons, R .

SCIENCE, 1997, 275 (5308) :1943-1947

[12] Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases [J].

Liliental, J ;

Moon, SY ;

Lesche, R ;

Mamillapalli, R ;

Li, DM ;

Zheng, Y ;

Sun, H ;

Wu, H .

CURRENT BIOLOGY, 2000, 10 (07) :401-404

[13] The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate [J].

Maehama, T ;

Dixon, JE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (22) :13375-13378

[14] PTEN and myotubularin: Novel phosphoinositide phosphatases [J].

Maehama, T ;

Taylor, GS ;

Dixon, JE .

ANNUAL REVIEW OF BIOCHEMISTRY, 2001, 70 :247-279

[15] The PTEN tumor suppressor homolog in Caenorhabditis elegans regulates longevity and dauer formation in an insulin receptor-like signaling pathway [J].

Mihaylova, VT ;

Borland, CZ ;

Manjarrez, L ;

Stern, MJ ;

Sun, H .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (13) :7427-7432

[16] Electrostatic control of the membrane targeting of C2 domains [J].

Murray, D ;

Honig, B .

MOLECULAR CELL, 2002, 9 (01) :145-154

[17] P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase [J].

Myers, MP ;

Stolarov, JP ;

Eng, C ;

Li, J ;

Wang, SI ;

Wigler, MH ;

Parsons, R ;

Tonks, NK .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (17) :9052-9057

[18] The lipid phosphatase activity of PTEN is critical for its tumor suppressor function [J].

Myers, MP ;

Pass, I ;

Batty, IH ;

Van der Kaay, J ;

Stolarov, JP ;

Hemmings, BA ;

Wigler, MH ;

Downes, CP ;

Tonks, NK .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (23) :13513-13518

[19] The role of phosphoinositide 3-kinase lipid products in cell function [J].

Rameh, LE ;

Cantley, LC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (13) :8347-8350

[20] Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN [J].

Tamura, M ;

Gu, JG ;

Matsumoto, K ;

Aota, S ;

Parsons, R ;

Yamada, KM .

SCIENCE, 1998, 280 (5369) :1614-1617