Journal article

The C-terminal tail inhibitory phosphorylation sites of PTEN regulate its intrinsic catalytic activity and the kinetics of its binding to phosphatidylinositol-4,5-bisphosphate

Yeong-Chit Joel Chia, Bruno Catimel, Daisy Sio Seng Lio, Ching-Seng Ang, Benjamin Peng, Hong Wu, Hong-Jian Zhu, Heung-Chin Cheng

Archives of Biochemistry and Biophysics | ELSEVIER SCIENCE INC | Published : 2015

Abstract

Dephosphorylation of four major C-terminal tail sites and occupancy of the phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]-binding site of PTEN cooperate to activate its phospholipid phosphatase activity and facilitate its recruitment to plasma membrane. Our investigation of the mechanism by which phosphorylation of these C-terminal sites controls the PI(4,5)P2-binding affinity and catalytic activity of PTEN resulted in the following findings. First, dephosphorylation of all four sites leads to full activation; and phosphorylation of any one site significantly reduces the intrinsic catalytic activity of PTEN. These findings suggest that coordinated inhibition of the upstream protein kinase..

View full abstract