P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase
AUTOR(ES)
Myers, Michael P.
FONTE
The National Academy of Sciences of the USA
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23024Documentos Relacionados
- Expression cloning of a human dual-specificity phosphatase.
- Overproduction, purification and structure determination of human dual-specificity phosphatase 14
- Functional cdc25C Dual-Specificity Phosphatase Is Required for S-Phase Entry in Human Cells
- Activation of the Jnk signaling pathway by a dual-specificity phosphatase, JSP-1
- A small CDC25 dual-specificity tyrosine-phosphatase isoform in Arabidopsis thaliana