Nature Cell Biology
7, 399 - 404 (2005)
Published online: 27 March 2005; | doi:10.1038/ncb1236
There is a Corrigendum (May 2005) associated with this Letter.
Regulation of PTEN by Rho small GTPasesZhong Li1, 5, Xuemei Dong1, 5, Zhenglong Wang1, 5, Wenzhong Liu1, Ning Deng3, Yu Ding3, Liuya Tang3, Tim Hla2, Rong Zeng3, Lin Li4
& Dianqing Wu11
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA. 2
Center for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA. 3
Research Center for Proteomics Analysis, Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. 4
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. 5
These authors contributed equally to this work.
Correspondence should be addressed to Dianqing Wu dwu@neuron.uchc.edu or Lin Li lli@sibs.ac.cnPTEN (phosphatase and tensin homologue) is a phosphatase that dephosphorylates both protein and phosphoinositide substrates. It is mutated in a variety of human tumours and has important roles in a diverse range of biological processes1,
2,
3,
4, including cell migration5,
6,
7 and chemotaxis8,
9. PTEN's intracellular localization and presumably activity are regulated by chemoattractants in Dictyostelium
10,
11 and mouse neutrophils12. However, the mechanisms for its regulation remain elusive. Here we show that RhoA and Cdc42, members of the Rho family of small GTPases13,
14,
15,
16, regulate the intracellular localization of PTEN in leukocytes and human transfected embryonic kidney cells. In addition, active RhoA is able to stimulate the phospholipid phosphatase activity of PTEN in human embryonic kidney cells and leukocytes, and this regulation seems to require RhoA's downstream effector, RhoA-associated kinase (Rock). Furthermore, we have identified key residues on PTEN that are required for its regulation by the small GTPase, and show that small GTPase-mediated regulation of PTEN has a significant role in the regulation of chemotaxis.
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