Adachi M, Ishino M, Torigoe T, Minami Y, Matozaki T, Miyazaki T, Taniguchi T, Hinoda Y, Imai K
First Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Oncogene. 1997 Apr 3;14(13):1629-33. doi: 10.1038/sj.onc.1200981.
Coupling of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) induces rapid increase in tyrosine phosphorylation of cellular substrates through activation of non-receptor protein tyrosine kinases. Here, we report that stimulation through the IL-2R induced tyrosine phosphorylation of the SH2-containing protein-tyrosine phosphatase SHP-2 in F7, a hematopoietic BAF-B03 transfectant clone expressing the IL-2Rbeta chain. The tyrosine phosphorylation of SHP-2 was specific since another protein-tyrosine phosphatase SHP-1, which is structurally homologous to SHP-2, was not tyrosine phosphorylated. The IL-2-induced tyrosine phosphorylation of SHP-2 required the acidic region within the IL-2Rbeta chain where Src-family PTKs interact. Though the serine-rich region within IL-2Rbeta chain was also required for the phosphorylation of SHP-2, Jak3 activation was dispensable. In COS-7 cells, co-expression of SHP-2 with Lyn resulted in increased tyrosine phosphorylation levels of SHP-2, whereas co-expression of SHP-2 with Fyn failed to alter the levels significantly. Considering that Lyn and Fyn are major Src-family PTKs expressed in BAF-B03 cells, our data suggest that Lyn may be principally responsible for the tyrosine phosphorylation of SHP-2 in F7 cells. Furthermore, the IL-2 stimulation also induced tyrosine phosphorylation of SHP-2 in the human IL-2-dependent T-cell line ILT-Mat. Taken together, these studies demonstrate an involvement of SHP-2 in the IL-2-mediated signaling events through the activation of specific PTKs.
白细胞介素-2（IL-2）与白细胞介素-2受体（IL-2R）的结合通过激活非受体蛋白酪氨酸激酶诱导细胞底物酪氨酸磷酸化迅速增加。在此，我们报告通过IL-2R刺激在F7（表达IL-2Rβ链的造血BAF-B03转染克隆）中诱导含SH2的蛋白酪氨酸磷酸酶SHP-2的酪氨酸磷酸化。SHP-2的酪氨酸磷酸化具有特异性，因为另一种与SHP-2结构同源的蛋白酪氨酸磷酸酶SHP-1未发生酪氨酸磷酸化。IL-2诱导的SHP-2酪氨酸磷酸化需要IL-2Rβ链内Src家族蛋白酪氨酸激酶（PTK）相互作用的酸性区域。虽然IL-2Rβ链内富含丝氨酸的区域对于SHP-2的磷酸化也是必需的，但Jak3激活并非必需。在COS-7细胞中，SHP-2与Lyn共表达导致SHP-2的酪氨酸磷酸化水平增加，而SHP-2与Fyn共表达未能显著改变该水平。鉴于Lyn和Fyn是在BAF-B03细胞中表达的主要Src家族PTK，我们的数据表明Lyn可能主要负责F7细胞中SHP-2的酪氨酸磷酸化。此外，IL-2刺激也在人IL-2依赖性T细胞系ILT-Mat中诱导SHP-2的酪氨酸磷酸化。综上所述，这些研究证明SHP-2通过特定PTK的激活参与IL-2介导的信号转导事件。
