Expanding coincident signaling by PTEN through its inositol 1,3,4,5,6‐pentakisphosphate 3‐phosphatase activity

FEBS Letters

Shears, Stephen B.³  Wenk, Markus R.²  Caffrey, James J.³  Darden, Tom¹ 

[1] Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA;Yale University School of Medicine, Department of Cell Biology, 295 Congress Avenue, New Haven, CT 06510, USA;Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

关键词: PTEN;    Phosphatidylinositol 3;    4;    5-trisphosphate;    Inositol 1;    3;    4;    5;    6-pentakisphosphate;    3-Phosphatase;    Inositol phosphate;   

DOI  :  10.1016/S0014-5793(01)02500-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

PTEN, a tumor suppressor among the most commonly mutated proteins in human cancer, is recognized to be both a protein phosphatase and a phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P₃) 3-phosphatase. Previous work [Maehama and Dixon, J. Biol. Chem. 273 (1998) 13375–13378] has led to a consensus that inositol phosphates are not physiologically relevant substrates for PTEN. In contrast, we demonstrate that PTEN is an active inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P₅) 3-phosphatase when expressed and purified from bacteria or HEK cells. Kinetic data indicate Ins(1,3,4,5,6)P₅ (K _m=7.1 μM) and PtdIns(3,4,5)P₃ (K _m=26 μM) compete for PTEN in vivo. Transient transfection of HEK cells with PTEN decreased Ins(1,3,4,5,6)P₅ levels. We discuss the physiological significance of these studies in relation to recent work showing that dephosphorylation of Ins(1,3,4,5,6)P₅ to inositol 1,4,5,6-tetrakisphosphate is a cell signaling event.

【 授权许可】

Unknown