Crystal structure of the PTEN tumor suppressor: Implications for its phosphoinositide phosphatase activity and membrane association Journal Article
| Authors: | Lee, J. O.; Yang, H.; Georgescu, M. M.; Cristofano, A. D.; Maehama, T.; Shi, Y.; Dixon, J. E.; Pandolfi, P.; Pavletich, N. P. |
| Article Title: | Crystal structure of the PTEN tumor suppressor: Implications for its phosphoinositide phosphatase activity and membrane association |
| 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. |
| Keywords: | controlled study; human cell; animals; phosphatase; carboxy terminal sequence; protein; drosophila; enzyme activity; tumor suppressor gene; amino acid sequence; molecular sequence data; sequence homology, amino acid; amino terminal sequence; sequence alignment; tumor suppressor proteins; pten phosphohydrolase; amino acid; crystal structure; models, molecular; crystallography, x-ray; binding sites; caenorhabditis elegans; protein structure; sequence homology; computer graphics; phosphoric monoester hydrolases; protein structure, secondary; genes, tumor suppressor; xenopus; phospholipid; polypeptide; membrane; phosphatidylinositide; phosphatidylinositols; humans; human; priority journal; article |
| Journal Title: | Cell |
| Volume: | 99 |
| Issue: | 3 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 1999-10-29 |
| Start Page: | 323 |
| End Page: | 334 |
| Language: | English |
| DOI: | 10.1016/s0092-8674(00)81663-3 |
| PUBMED: | 10555148 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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