title: Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T.
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.
authors.affiliation: Department of Genetics and Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Ailan
authors.initials: A
authors.lastname: Guo
authors.forename: Jianshi
authors.initials: J
authors.lastname: Yu
authors.forename: Anthony
authors.initials: A
authors.lastname: Possemato
authors.forename: Yueting
authors.initials: Y
authors.lastname: Chen
authors.forename: Weiping
authors.initials: W
authors.lastname: Zheng
authors.forename: Roberto D
authors.initials: RD
authors.lastname: Polakiewicz
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Victor E
authors.initials: VE
authors.lastname: Velculescu
authors.forename: Zhenghe John
authors.initials: ZJ
authors.lastname: Wang
mesh_terms: 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
chemical_list: 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