Fujioka Y, Matozaki T, Noguchi T, Iwamatsu A, Yamao T, Takahashi N, Tsuda M, Takada T, Kasuga M
Second Department of Internal Medicine, Kobe University School of Medicine, Chuo-ku, Japan.
Mol Cell Biol. 1996 Dec;16(12):6887-99. doi: 10.1128/MCB.16.12.6887.
Protein tyrosine phosphatases (PTPases), such as SHP-1 and SHP-2, that contain Src homology 2 (SH2) domains play important roles in growth factor and cytokine signal transduction pathways. A protein of approximately 115 to 120 kDa that interacts with SHP-1 and SHP-2 was purified from v-src-transformed rat fibroblasts (SR-3Y1 cells), and the corresponding cDNA was cloned. The predicted amino acid sequence of the encoded protein, termed SHPS-1 (SHP substrate 1), suggests that it is a glycosylated receptor-like protein with three immunoglobulin-like domains in its extracellular region and four YXX(L/V/I) motifs, potential tyrosine phosphorylation and SH2-domain binding sites, in its cytoplasmic region. Various mitogens, including serum, insulin, and lysophosphatidic acid, or cell adhesion induced tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2 in cultured cells. Thus, SHPS-1 may be a direct substrate for both tyrosine kinases, such as the insulin receptor kinase or Src, and a specific docking protein for SH2-domain-containing PTPases. In addition, we suggest that SHPS-1 may be a potential substrate for SHP-2 and may function in both growth factor- and cell adhesion-induced cell signaling.
蛋白质酪氨酸磷酸酶（PTPases），如含Src同源2（SH2）结构域的SHP-1和SHP-2，在生长因子和细胞因子信号转导途径中发挥重要作用。从v-src转化的大鼠成纤维细胞（SR-3Y1细胞）中纯化出一种与SHP-1和SHP-2相互作用的约115至120 kDa的蛋白质，并克隆了相应的cDNA。编码蛋白（称为SHPS-1，即SHP底物1）的预测氨基酸序列表明，它是一种糖基化的受体样蛋白，其细胞外区域有三个免疫球蛋白样结构域，细胞质区域有四个YXX(L/V/I)基序，即潜在的酪氨酸磷酸化和SH2结构域结合位点。包括血清、胰岛素和溶血磷脂酸在内的各种促有丝分裂原，或细胞黏附，均可诱导培养细胞中SHPS-1的酪氨酸磷酸化及其随后与SHP-2的结合。因此，SHPS-1可能既是酪氨酸激酶（如胰岛素受体激酶或Src）的直接底物，也是含SH2结构域的PTPases的特异性对接蛋白。此外，我们认为SHPS-1可能是SHP-2的潜在底物，并可能在生长因子和细胞黏附诱导的细胞信号传导中发挥作用。
