Mathews S T, Srinivas P R, Leon M A, Grunberger G
Department of Internal Medicine, Wayne State University, Detroit, MI 48201, USA.
Life Sci. 1997;61(16):1583-92. doi: 10.1016/s0024-3205(97)00737-6.
Fetuin has been identified earlier as the bovine homolog of the human plasma protein, alpha2-Heremans Schmid glycoprotein (alpha2-HSG). Although bovine fetuin shares over 70% amino acid sequence similarity with alpha2-HSG and rat fetuin, no common function(s) have been identified. We report that immunoaffinity purified bovine fetuin acts as an inhibitor of insulin receptor tyrosine kinase activity (IR-TKA) with half-maximal inhibition at 1.5 microM. In vitro, bovine fetuin (1.5 microM) blocked insulin-induced autophosphorylation of the human IR completely and the half-maximal inhibitory effect was observed at 0.5 microM. Incubation of HIRcB cells (rat1 fibroblasts transfected with wild-type human insulin receptor cDNA) with bovine fetuin (1.5 microM) inhibited insulin-induced tyrosine phosphorylation of the IR beta-subunit by 40%. In addition, bovine fetuin (2 microM) completely blocked insulin-stimulated DNA synthesis in H-35 rat hepatoma cells. Our results, together with earlier reports on rat fetuin and human alpha2-HSG, indicate a common IR-TK inhibitory function for fetuin homologs.
胎球蛋白早期被鉴定为人类血浆蛋白α2-赫雷曼斯·施密德糖蛋白（α2-HSG）的牛同源物。尽管牛胎球蛋白与α2-HSG和大鼠胎球蛋白的氨基酸序列相似度超过70%，但尚未发现它们有共同的功能。我们报告称，免疫亲和纯化的牛胎球蛋白可作为胰岛素受体酪氨酸激酶活性（IR-TKA）的抑制剂，在1.5微摩尔时具有半数最大抑制作用。在体外，牛胎球蛋白（1.5微摩尔）可完全阻断胰岛素诱导的人胰岛素受体自磷酸化，在0.5微摩尔时观察到半数最大抑制作用。用牛胎球蛋白（1.5微摩尔）孵育HIRcB细胞（转染了野生型人胰岛素受体cDNA的大鼠1成纤维细胞）可使胰岛素诱导的胰岛素受体β亚基酪氨酸磷酸化抑制40%。此外，牛胎球蛋白（2微摩尔）可完全阻断胰岛素刺激的H-35大鼠肝癌细胞中的DNA合成。我们的结果，连同早期关于大鼠胎球蛋白和人α2-HSG的报道，表明胎球蛋白同源物具有共同的IR-TK抑制功能。
