Beauchemin N, Kunath T, Robitaille J, Chow B, Turbide C, Daniels E, Veillette A
McGill Cancer Centre, Department of Biochemistry, McGill University, Montréal, Québec, Canada.
Oncogene. 1997 Feb 20;14(7):783-90. doi: 10.1038/sj.onc.1200888.
Biliary glycoprotein (Bgp) is a member of the immunoglobulin superfamily and the carcinoembryonic antigen family. Previous studies have shown that Bgp functions as an intercellular adhesion molecule and a canalicular bile salt transporter. Moreover, we and others demonstrated that Bgp can inhibit colonic and prostatic tumor cell growth in vivo, through a mechanism which depends on sequences present in its cytoplasmic domain. In this study, we have examined the possibility that the cytoplasmic domain of Bgp can interact with signal transduction molecules. We showed that tyrosine phosphorylated Bgp, expressed in mouse colon carcinoma CT51 cells, could reversibly associate with protein tyrosine phosphatase SHP-1. Mutation of either of two tyrosine residues present in the cytoplasmic domain of Bgp abrogated SHP-1 binding, suggesting that this association was mediated by both tyrosine residues. Similarly, we noted that either of the two SH2 domains of SHP-1 could bind tyrosine phosphorylated Bgp in vitro. It is therefore conceivable that some of the functions of Bgp are mediated through its ability to induce intracellular protein tyrosine dephosphorylation.
胆汁糖蛋白（Bgp）是免疫球蛋白超家族和癌胚抗原家族的成员。先前的研究表明，Bgp作为一种细胞间粘附分子和胆小管胆汁盐转运体发挥作用。此外，我们和其他人证明，Bgp可以通过一种依赖于其细胞质结构域中存在的序列的机制在体内抑制结肠和前列腺肿瘤细胞的生长。在本研究中，我们研究了Bgp细胞质结构域与信号转导分子相互作用的可能性。我们发现，在小鼠结肠癌CT51细胞中表达的酪氨酸磷酸化Bgp可以与蛋白酪氨酸磷酸酶SHP-1可逆性结合。Bgp细胞质结构域中存在的两个酪氨酸残基中的任何一个发生突变都会消除SHP-1的结合，这表明这种结合是由两个酪氨酸残基介导的。同样，我们注意到SHP-1的两个SH2结构域中的任何一个在体外都可以结合酪氨酸磷酸化的Bgp。因此可以设想，Bgp的一些功能是通过其诱导细胞内蛋白酪氨酸去磷酸化的能力介导的。
