title: P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase.
abstract: 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.
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Myers
authors.forename: J P
authors.initials: JP
authors.lastname: Stolarov
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: S I
authors.initials: SI
authors.lastname: Wang
authors.forename: M H
authors.initials: MH
authors.lastname: Wigler
authors.forename: R
authors.initials: R
authors.lastname: Parsons
authors.forename: N K
authors.initials: NK
authors.lastname: Tonks
mesh_terms: D000595:Amino Acid Sequence; D002879:Chromosomes, Human, Pair 10; D004789:Enzyme Activation; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase