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 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.
Zhang
Xiaodong
X
Department of Genetics and Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Guo
Ailan
A
Yu
Jianshi
J
Possemato
Anthony
A
Chen
Yueting
Y
Zheng
Weiping
W
Polakiewicz
Roberto D
RD
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
Velculescu
Victor E
VE
Wang
Zhenghe John
ZJ
D002460:Cell Line; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D013379:Substrate Specificity; D014443:Tyrosine / Q000737:chemistry
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014443:Tyrosine; D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases; C516865:PTPRT protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2