P-TEN, the Tumor Suppressor from Human Chromosome 10q23, is a Dual-Specificity Phosphatase
Protein tyrosine phosphatases (PTPs) have long been thought to play a role in tumor suppression due to their ability to antagonize the growth promoting protein tyrosine kinases. Recently, a candidate tumor suppressor from 10q23, termed P-TEN, was isolated, and sequence homology was demonstrated with...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1997-08, Vol.94 (17), p.9052-9057 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Myers, Michael P. Stolarov, Javor P. Eng, Charis Li, Jing Wang, Steven I. Wigler, Michael H. Parsons, Ramon Tonks, Nicholas K. |
| description | Protein tyrosine phosphatases (PTPs) have long been thought to play a role in tumor suppression due to their ability to antagonize the growth promoting protein tyrosine kinases. Recently, a candidate tumor suppressor from 10q23, termed P-TEN, was isolated, and sequence homology was demonstrated with members of the PTP family, as well as the cytoskeletal protein tensin. Here we show that recombinant P-TEN dephosphorylated protein and peptide substrates phosphorylated on serine, threonine, and tyrosine residues, indicating that P-TEN is a dual-specificity phosphatase. In addition, P-TEN exhibited a high degree of substrate specificity, showing selectivity for extremely acidic substrates in vitro. Furthermore, we demonstrate that mutations in P-TEN, identified from primary tumors, tumor cells lines, and a patient with Bannayan-Zonana syndrome, resulted in the ablation of phosphatase activity, demonstrating that enzymatic activity of P-TEN is necessary for its ability to function as a tumor suppressor. |
| doi_str_mv | 10.1073/pnas.94.17.9052 |
| format | Article |
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Recently, a candidate tumor suppressor from 10q23, termed P-TEN, was isolated, and sequence homology was demonstrated with members of the PTP family, as well as the cytoskeletal protein tensin. Here we show that recombinant P-TEN dephosphorylated protein and peptide substrates phosphorylated on serine, threonine, and tyrosine residues, indicating that P-TEN is a dual-specificity phosphatase. In addition, P-TEN exhibited a high degree of substrate specificity, showing selectivity for extremely acidic substrates in vitro. Furthermore, we demonstrate that mutations in P-TEN, identified from primary tumors, tumor cells lines, and a patient with Bannayan-Zonana syndrome, resulted in the ablation of phosphatase activity, demonstrating that enzymatic activity of P-TEN is necessary for its ability to function as a tumor suppressor.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.94.17.9052</identifier><identifier>PMID: 9256433</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Amino Acid Sequence ; Amino acids ; Biochemistry ; Biological Sciences ; Chromosomes, Human, Pair 10 ; Enzyme Activation ; Enzymes ; Genes, Tumor Suppressor ; Genetic mutation ; Glioblastoma ; Humans ; Molecular biology ; Molecular Sequence Data ; Multiple hamartoma syndrome ; Mutation ; Peptides ; Phosphatases ; Phosphates ; Phosphoprotein Phosphatases - genetics ; Phosphoprotein Phosphatases - metabolism ; Phosphorylation ; Point mutation ; Protein Tyrosine Phosphatases - genetics ; Protein Tyrosine Phosphatases - metabolism ; Proteins ; PTEN Phosphohydrolase ; Substrate Specificity ; Tumors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1997-08, Vol.94 (17), p.9052-9057</ispartof><rights>Copyright 1997 National Academy of Sciences</rights><rights>Copyright National Academy of Sciences Aug 19, 1997</rights><rights>Copyright © 1997, The National Academy of Sciences of the USA 1997</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c584t-9223a2efd6c0eb53bd3656587af0276677e0881fd2eb6f56dd035b1e344bbf6f3</citedby><cites>FETCH-LOGICAL-c584t-9223a2efd6c0eb53bd3656587af0276677e0881fd2eb6f56dd035b1e344bbf6f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/94/17.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/42555$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/42555$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9256433$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Myers, Michael P.</creatorcontrib><creatorcontrib>Stolarov, Javor P.</creatorcontrib><creatorcontrib>Eng, Charis</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Wang, Steven I.</creatorcontrib><creatorcontrib>Wigler, Michael H.</creatorcontrib><creatorcontrib>Parsons, Ramon</creatorcontrib><creatorcontrib>Tonks, Nicholas K.</creatorcontrib><title>P-TEN, the Tumor Suppressor from Human Chromosome 10q23, is a Dual-Specificity Phosphatase</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Protein tyrosine phosphatases (PTPs) have long been thought to play a role in tumor suppression due to their ability to antagonize the growth promoting protein tyrosine kinases. 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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1997-08, Vol.94 (17), p.9052-9057 |
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| subjects | Amino Acid Sequence Amino acids Biochemistry Biological Sciences Chromosomes, Human, Pair 10 Enzyme Activation Enzymes Genes, Tumor Suppressor Genetic mutation Glioblastoma Humans Molecular biology Molecular Sequence Data Multiple hamartoma syndrome Mutation Peptides Phosphatases Phosphates Phosphoprotein Phosphatases - genetics Phosphoprotein Phosphatases - metabolism Phosphorylation Point mutation Protein Tyrosine Phosphatases - genetics Protein Tyrosine Phosphatases - metabolism Proteins PTEN Phosphohydrolase Substrate Specificity Tumors |
| title | P-TEN, the Tumor Suppressor from Human Chromosome 10q23, is a Dual-Specificity Phosphatase |
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