P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase

被引:690
作者
Myers, MP
Stolarov, JP
Eng, C
Li, J
Wang, SI
Wigler, MH
Parsons, R
Tonks, NK
机构
[1] COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724
[2] HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115
[3] COLUMBIA UNIV COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY 10032
[4] COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032
关键词
cancer; tyrosine phosphorylation; signal transduction; protein tyrosine phosphatase;
D O I
10.1073/pnas.94.17.9052
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 via a. Furthermore, Ive 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.
引用
收藏
页码:9052 / 9057
页数:6
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