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 growt h promoting protein tyrosine kinases. Recently, a candidate tumor supp ressor from 10q23, termed P-TEN, was isolated, and sequence homology w as demonstrated with members of the PTP family, as well as the cytoske letal protein tensin. Here we show that recombinant P-TEN dephosphoryl ated protein and peptide substrates phosphorylated on serine, threonin e, and tyrosine residues, indicating that P-TEN is a dual-specificity phosphatase. In addition, P-TEN exhibited a high degree of substrate s pecificity, showing selectivity for extremely acidic substrates in via a. Furthermore, Ive demonstrate that mutations in P-TEN, identified f rom primary tumors, tumor cells lines, and a patient with Bannayan-Zon ana syndrome, resulted in the ablation of phosphatase activity, demons trating that enzymatic activity of P-TEN is necessary for its ability to function as a tumor suppressor.