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

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...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2007-03, Vol.104 (10), p.4060-4064
Main Authors: Zhang, Xiaodong, Guo, Ailan, Yu, Jianshi, Possemato, Anthony, Chen, Yueting, Zheng, Weiping, Polakiewicz, Roberto D, Kinzler, Kenneth W, Vogelstein, Bert, Velculescu, Victor E, Wang, Zhenghe John
Format: Article
Language:English
Subjects:
Amino acids
Antibodies
Biochemistry
Biological Sciences
Cell growth
Cell Line
Cell Line, Tumor
Cell lines
Colorectal cancer
Colorectal Neoplasms - metabolism
Epithelial cells
Gene expression
Gene expression regulation
Gene Expression Regulation, Neoplastic
Glutathione Transferase - metabolism
HCT116 cells
HEK293 cells
Humans
Mutation
Phosphatases
Phosphorus
Phosphorylation
Protein Binding
Protein-Tyrosine Kinases - metabolism
Proteins
Receptor-Like Protein Tyrosine Phosphatases, Class 2
Signal Transduction
STAT3 Transcription Factor - chemistry
STAT3 Transcription Factor - physiology
Substrate Specificity
T lymphocytes
Tumors
Tyrosine - chemistry
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0611665104