Liu F, Chernoff J
Chemistry Department, Temple University, Philadelphia, PA 19122, USA.
Biochem J. 1997 Oct 1;327 ( Pt 1)(Pt 1):139-45. doi: 10.1042/bj3270139.
We used a substrate-trapping technique to search for substrates of protein tyrosine phosphatase (PTP) 1B. A catalytically inactive form of this enzyme forms a stable, phosphotyrosine-dependent complex with epidermal growth factor receptor (EGFR) both in vitro and in cells. PTP1B also interacts with activated platelet-derived growth factor receptor (PDGFR) but not with colony-stimulating factor 1 receptor (CSF-1R). After binding to EGFR, PTP1B becomes tyrosine-phosphorylated at Tyr-66, a site that conforms to the consensus binding sequence for the Src homology 2 (SH2) domains of the adapter protein Grb2. This tyrosine phosphorylation is correlated with a 3-fold increase in PTP catalytic activity. These findings suggest that PTP1B selectively regulates specific activated receptor protein tyrosine kinases (RPTKs) in vivo and might itself be regulated by such receptors.
我们采用底物捕获技术来寻找蛋白酪氨酸磷酸酶（PTP）1B的底物。该酶的催化失活形式在体外和细胞内均能与表皮生长因子受体（EGFR）形成稳定的、依赖磷酸酪氨酸的复合物。PTP1B还能与活化的血小板衍生生长因子受体（PDGFR）相互作用，但不与集落刺激因子1受体（CSF-1R）相互作用。与EGFR结合后，PTP1B在Tyr-66位点发生酪氨酸磷酸化，该位点符合衔接蛋白Grb2的Src同源2（SH2）结构域的共有结合序列。这种酪氨酸磷酸化与PTP催化活性增加3倍相关。这些发现表明，PTP1B在体内选择性地调节特定的活化受体蛋白酪氨酸激酶（RPTK），其自身可能也受此类受体的调节。
