Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4060-4064
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number10
DOIs
StatePublished - Mar 6 2007

Keywords

  • Colorectal cancer
  • Signaling
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • General

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