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
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
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Awarded by National Health and Medical Research Council of Australia
The work described in this manuscript was supported by project grants from the National Health and Medical Research Council of Australia (APP1050486) and Australian Research Council (to H.-C.C., H.-J. Z. and B.C.).