PTEN dephosphorylates PIP3

Stable Identifier
Reaction [transition]
Homo sapiens
PI(3,4,5)P3 is dephosphorylated to PI (4,5)P2 by PTEN at the plasma membrane
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At the plasma membrane, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase aka phosphatase and tensin homolog (PTEN) dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) (Maehama & Dixon 1998, Myers et al. 1998, Das et al. 2003). The PI3K network is negatively regulated by phospholipid phosphatases that dephosphorylate PIP3, thus hampering AKT activation (Myers et al. 1998). The tumour suppressor PTEN is the primary phospholipid phosphatase.
Early studies indicated that magnesium ion, Mg2+, was needed for the catalytic activity of PTEN isolated from bovine thymus (Kabuyama et al. 1996). Subsequent studies have shown that PTEN was catalytically active in buffers free of magnesium and magnesium was not detected as part of the PTEN crystal (Lee et al. 1999).

Literature References
PubMed ID Title Journal Year
10555148 Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association

Georgescu, MM, Pavletich, NP, Shi, Y, Maehama, T, Pandolfi, P, Yang, H, Lee, JO, Dixon, JE, Di Cristofano, A

Cell 1999
12808147 Membrane-binding and activation mechanism of PTEN

Das, S, Cho, W, Dixon, JE

Proc Natl Acad Sci U S A 2003
9593664 The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate

Dixon, JE, Maehama, T

J Biol Chem 1998
9811831 The lipid phosphatase activity of PTEN is critical for its tumor supressor function

Stolarov, JP, van der Kaay, J, Myers, MP, Pass, I, Downes, CP, Batty, IH, Wigler, MH, Tonks, NK, Hemmings, BA

Proc Natl Acad Sci U S A 1998
8681945 Purification and characterization of the phosphatidylinositol-3,4,5-trisphosphate phosphatase in bovine thymus

Fukui, Y, Kabuyama, Y, Homma, Y, Nakatsu, N

Eur. J. Biochem. 1996
Event Information
Catalyst Activity

phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity of PTEN [cytosol]

Orthologous Events
Cross References
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