Crystal structure of the PTEN tumor suppressor: Implications for its phosphoinositide phosphatase activity and membrane association

Jie Oh Lee, Haijuan Yang, Maria Magdalena Georgescu, Antonio Di Cristofano, Tomohiko Maehama, Yigong Shi, Jack E. Dixon, Pier Pandolfi, Nikola P. Pavletich

Research output: Contribution to journalArticle

752 Citations (Scopus)

Abstract

The PTEN tumor suppressor is mutated in diverse human cancers and in hereditary cancer predisposition syndromes. PTEN is a phosphatase that can act on both polypeptide and phosphoinositide substrates in vitro. The PTEN structure reveals a phosphatase domain that is similar to protein phosphatases but has an enlarged active site important for the accommodation of the phosphoinositide substrate. The structure also reveals that PTEN has a C2 domain. The PTEN C2 domain binds phospholipid membranes in vitro, and mutation of basic residues that could mediate this reduces PTEN's membrane affinity and its ability to suppress the growth of glioblastoma tumor cells. The phosphatase and C2 domains associate across an extensive interface, suggesting that the C2 domain may serve to productively position the catalytic domain on the membrane.

Original languageEnglish (US)
Pages (from-to)323-334
Number of pages12
JournalCell
Volume99
Issue number3
DOIs
StatePublished - Oct 29 1999
Externally publishedYes

Fingerprint

Phosphatidylinositols
Phosphoric Monoester Hydrolases
Tumors
Crystal structure
Membranes
Catalytic Domain
Neoplasms
Hereditary Neoplastic Syndromes
Phosphoprotein Phosphatases
Substrates
Phospholipids
Glioblastoma
Cells
Peptides
Mutation
Phosphoinositide Phosphatases
C2 Domains
Growth
In Vitro Techniques

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Crystal structure of the PTEN tumor suppressor : Implications for its phosphoinositide phosphatase activity and membrane association. / Lee, Jie Oh; Yang, Haijuan; Georgescu, Maria Magdalena; Di Cristofano, Antonio; Maehama, Tomohiko; Shi, Yigong; Dixon, Jack E.; Pandolfi, Pier; Pavletich, Nikola P.

In: Cell, Vol. 99, No. 3, 29.10.1999, p. 323-334.

Research output: Contribution to journalArticle

Lee, JO, Yang, H, Georgescu, MM, Di Cristofano, A, Maehama, T, Shi, Y, Dixon, JE, Pandolfi, P & Pavletich, NP 1999, 'Crystal structure of the PTEN tumor suppressor: Implications for its phosphoinositide phosphatase activity and membrane association', Cell, vol. 99, no. 3, pp. 323-334. https://doi.org/10.1016/S0092-8674(00)81663-3
Lee, Jie Oh ; Yang, Haijuan ; Georgescu, Maria Magdalena ; Di Cristofano, Antonio ; Maehama, Tomohiko ; Shi, Yigong ; Dixon, Jack E. ; Pandolfi, Pier ; Pavletich, Nikola P. / Crystal structure of the PTEN tumor suppressor : Implications for its phosphoinositide phosphatase activity and membrane association. In: Cell. 1999 ; Vol. 99, No. 3. pp. 323-334.
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AU - Di Cristofano, Antonio

AU - Maehama, Tomohiko

AU - Shi, Yigong

AU - Dixon, Jack E.

AU - Pandolfi, Pier

AU - Pavletich, Nikola P.

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