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Chemical and structural approaches to investigate PTEN function and regulation.

ABSTRACT: Phosphatase and tensin homolog is a lipid phosphatase that serves as the major negative regulator of the PI3K/AKT pathway. It catalyzes the 3'-specific dephosphorylation of phosphatidylinositol (3,4,5)-trisphosphate (PIP₃) to generate PIP₂. PTEN's lipid phosphatase function depends on several domains, including an N-terminal segment spanning the first 24 amino acids, which results in a catalytically impaired enzyme when mutated. Furthermore, PTEN is regulated by a cluster of phosphorylation sites located on its C-terminal tail at Ser380, Thr382, Thr383, and Ser385, which drives its conformation from an open to a closed autoinhibited but stable state. Herein, we discuss the protein chemical strategies we used to reveal the structure and mechanism of how PTEN's terminal regions govern its function.

SUBMITTER: Viennet T

PROVIDER: S-EPMC10037535 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Chemical and structural approaches to investigate PTEN function and regulation.

Viennet Thibault T Rodriguez Ospina Santiago S Lu Yunqi Y Cui Anna A Arthanari Haribabu H Dempsey Daniel R DR

Methods in enzymology 20221224

Phosphatase and tensin homolog is a lipid phosphatase that serves as the major negative regulator of the PI3K/AKT pathway. It catalyzes the 3'-specific dephosphorylation of phosphatidylinositol (3,4,5)-trisphosphate (PIP<sub>3</sub>) to generate PIP<sub>2</sub>. PTEN's lipid phosphatase function depends on several domains, including an N-terminal segment spanning the first 24 amino acids, which results in a catalytically impaired enzyme when mutated. Furthermore, PTEN is regulated by a cluster o ...[more]

PMID: 36948705

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