King A G, Ozanne B W, Smythe C, Ashworth A
Cancer-Research Campaign Laboratories, Beatson Institute for Cancer Research, Garscube Estate, Bearsden, UK.
Oncogene. 1995 Dec 21;11(12):2553-63.
The recent discovery of the vaccinia virus protein phosphatase VH1, and its mammalian counterparts has highlighted a novel subfamily of protein tyrosine phosphatases that exhibit dual specificity toward phosphotyrosine- and phosphoserine/threonine-residues. We have identified further members of this subfamily. The characterisation of one clone in particular, which we have named threonine-tyrosine phosphatase 1 (TYP 1), encodes a protein homologous to CL100, but differs dramatically in its regulation. TYP 1 is not expressed in human fibroblasts unlike other CL100-like genes. Furthermore, northern analysis has demonstrated that following mitogenic stimulation of squamous cells, induction of TYP 1 mRNA reaches its maximal levels after four hours, in contrast to the immediate early CL100-like genes. Both TYP 1 and CL100 mRNAs are induced upon TGF-beta treatment of squamous cell lines sensitive to the growth factors antiproliferative effects. When TYP 1 is transfected into COS-1 cells, the gene product inhibits both ERK2 and p54 MAP kinase subfamilies. In addition, we show that purified TYP 1 protein efficiently inactivates recombinant ERK2 in vitro by the concomitant dephosphorylation of both its phosphothreonine and -tyrosine residues. TYP 1 encodes a nuclear protein, which when expressed in COS cells is stabilised by EGF treatment.
痘苗病毒蛋白磷酸酶VH1及其哺乳动物对应物的最新发现，凸显了一类新型蛋白酪氨酸磷酸酶亚家族，该亚家族对磷酸酪氨酸和磷酸丝氨酸/苏氨酸残基具有双重特异性。我们已经鉴定出该亚家族的其他成员。特别是对一个克隆的表征，我们将其命名为苏氨酸 - 酪氨酸磷酸酶1（TYP 1），它编码一种与CL100同源的蛋白质，但其调节方式却有很大不同。与其他CL100样基因不同，TYP 1在人成纤维细胞中不表达。此外，Northern分析表明，在对鳞状细胞进行促有丝分裂刺激后，TYP 1 mRNA的诱导在4小时后达到最高水平，这与立即早期的CL100样基因形成对比。在用TGF-β处理对生长因子抗增殖作用敏感的鳞状细胞系时，TYP 1和CL100的mRNA均被诱导。当TYP 1转染到COS-1细胞中时，该基因产物抑制ERK2和p54 MAP激酶亚家族。此外，我们表明纯化的TYP 1蛋白在体外通过同时去磷酸化其磷酸苏氨酸和磷酸酪氨酸残基有效地使重组ERK2失活。TYP 1编码一种核蛋白，当在COS细胞中表达时，通过EGF处理使其稳定。
