Identification of STAT3 As a Substrate of Receptor Protein Tyrosine Phosphatase T

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Mar 16

PMID 17360477

Citations 113

Authors

Xiaodong Zhang

Ailan Guo

Jianshi Yu

Anthony Possemato

Yueting Chen

Weiping Zheng

Roberto D Polakiewicz

Kenneth W Kinzler

Bert Vogelstein

Victor E Velculescu

Zhenghe John Wang

Affiliations

Soon will be listed here.

Abstract

Protein tyrosine phosphatase (PTP) receptor T (PTPRT) is the most frequently mutated PTP in human cancers. However, the cell signaling pathways regulated by PTPRT have not yet been elucidated. Here, we report identification of signal transducer and activator of transcription 3 (STAT3) as a substrate of PTPRT. Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position. Accordingly, overexpression of normal PTPRT in colorectal cancer cells reduced the expression of STAT3 target genes. These studies illuminate a mechanism regulating the STAT3 pathway and suggest that this signaling pathway plays an important role in colorectal tumorigenesis.

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