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 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.
Myers
M P
MP
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Stolarov
J P
JP
Eng
C
C
Li
J
J
Wang
S I
SI
Wigler
M H
MH
Parsons
R
R
Tonks
N K
NK
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
D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase