PTEN as an effector in the signaling of antimigratory G protein-coupled receptor.
作者： T. Sanchez , S. Thangada , M.-T. Wu , C. D. Kontos , D. Wu
关键词:
摘要: PTEN, a tumor suppressor phosphatase, is important in the regulation of cell migration and invasion. Physiological PTEN (phosphatase tensin homolog deleted on chromosome 10) by surface receptors has not been described. Here, we show that bioactive lipid sphingosine 1-phosphate (S1P), which acts through S1P2 receptor (S1P2R) G protein-coupled (GPCR) to inhibit migration, utilizes as signaling intermediate. S1P2R inhibition abrogated dominant-negative expression. S1P was unable efficiently Pten(DeltaloxP/DeltaloxP) mouse embryonic fibroblasts; however, antimigratory effect restored upon expression PTEN. activation Rho GTPase affected cells, reversed WT cells but suggesting downstream GTPase. Ligand stimulated coimmunoprecipitation Interestingly, increased phosphatase activity membrane fractions. Furthermore, tyrosine phosphorylation signaling. These data suggest actively regulates GTPase-dependent pathway migration. GPCR maybe general mechanism events
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sci-hub.se 参考文章(51)
Menq-Jer Lee, James R Van Brocklyn, Shobha Thangada, Catherine H Liu, Arthur R Hand, Ramil Menzeleev, Sarah Spiegel, Timothy Hla, Sphingosine-1-Phosphate as a Ligand for the G Protein-Coupled Receptor EDG-1 Science. ,vol. 279, pp. 1552- 1555 ,(1998) , 10.1126/SCIENCE.279.5356.1552
T Hla, T Maciag, An abundant transcript induced in differentiating human endothelial cells encodes a polypeptide with structural similarities to G-protein-coupled receptors. Journal of Biological Chemistry. ,vol. 265, pp. 9308- 9313 ,(1990) , 10.1016/S0021-9258(19)38849-0
Jie-Oh Lee, Haijuan Yang, Maria-Magdalena Georgescu, Antonio Di Cristofano, Tomohiko Maehama, Yigong Shi, Jack E Dixon, Pier Pandolfi, Nikola P Pavletich, Crystal Structure of the PTEN Tumor Suppressor: Implications for Its Phosphoinositide Phosphatase Activity and Membrane Association Cell. ,vol. 99, pp. 323- 334 ,(1999) , 10.1016/S0092-8674(00)81663-3
C Chen, H Okayama, High-efficiency transformation of mammalian cells by plasmid DNA. Molecular and Cellular Biology. ,vol. 7, pp. 2745- 2752 ,(1987) , 10.1128/MCB.7.8.2745
Menq-Jer Lee, Shobha Thangada, Ji-Hye Paik, Gopal P. Sapkota, Nicolas Ancellin, Sung-Suk Chae, Mingtao Wu, Manuel Morales-Ruiz, William C. Sessa, Dario R. Alessi, Timothy Hla, Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis Molecular Cell. ,vol. 8, pp. 693- 704 ,(2001) , 10.1016/S1097-2765(01)00324-0
Nicolas Ancellin, Timothy Hla, Differential Pharmacological Properties and Signal Transduction of the Sphingosine 1-Phosphate Receptors EDG-1, EDG-3, and EDG-5 Journal of Biological Chemistry. ,vol. 274, pp. 18997- 19002 ,(1999) , 10.1074/JBC.274.27.18997
Jianhua Huang, Christopher D. Kontos, PTEN Modulates Vascular Endothelial Growth Factor-Mediated Signaling and Angiogenic Effects Journal of Biological Chemistry. ,vol. 277, pp. 10760- 10766 ,(2002) , 10.1074/JBC.M110219200
Menq-Jer Lee, Mark Evans, Timothy Hla, THE INDUCIBLE G PROTEIN-COUPLED RECEPTOR EDG-1 SIGNALS VIA THE GI/MITOGEN-ACTIVATED PROTEIN KINASE PATHWAY Journal of Biological Chemistry. ,vol. 271, pp. 11272- 11279 ,(1996) , 10.1074/JBC.271.19.11272
Vuk Stambolic, Akira Suzuki, José Luis de la Pompa, Greg M Brothers, Christine Mirtsos, Takehiko Sasaki, Jurgen Ruland, Josef M Penninger, David P Siderovski, Tak W Mak, Negative Regulation of PKB/Akt-Dependent Cell Survival by the Tumor Suppressor PTEN Cell. ,vol. 95, pp. 29- 39 ,(1998) , 10.1016/S0092-8674(00)81780-8
M.-M. Georgescu, K. H. Kirsch, T. Akagi, T. Shishido, H. Hanafusa, The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region Proceedings of the National Academy of Sciences. ,vol. 96, pp. 10182- 10187 ,(1999) , 10.1073/PNAS.96.18.10182