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
Department of Genetics and Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4060-4. doi: 10.1073/pnas.0611665104. Epub 2007 Feb 21.
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.
蛋白酪氨酸磷酸酶（PTP）受体T（PTPRT）是人类癌症中最常发生突变的PTP。然而，PTPRT所调控的细胞信号通路尚未阐明。在此，我们报告鉴定出信号转导及转录激活因子3（STAT3）是PTPRT的一个底物。氨基酸Y705处酪氨酸的磷酸化对于STAT3的功能至关重要，而PTPRT特异性地使该位置的STAT3去磷酸化。因此，在结肠癌细胞中过表达正常的PTPRT会降低STAT3靶基因的表达。这些研究揭示了一种调控STAT3通路的机制，并表明该信号通路在结肠肿瘤发生中起重要作用。
