Lu Q, Mukhopadhyay N K, Griffin J D, Paredes M, Medina M, Kosik K S
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
J Neurosci Res. 2002 Mar 1;67(5):618-24. doi: 10.1002/jnr.10151.
delta-Catenin associates with adhesive junctions and facilitates cellular morphogenesis (Lu et al., 1999). Here we show that delta-catenin colocalizes with actin filaments and Abl tyrosine kinase in the growth cones of cultured hippocampal neurons. PC12 cells induced to express delta-catenin show accelerated neurite extension upon nerve growth factor (NGF) stimulation. STI571, an Abl family kinase inhibitor, further accentuates these stimulatory effects. delta-Catenin is a potent substrate for Abl in vitro using an immunocomplex assay and most of the Abl-induced tyrosine phosphorylation within cells is present in the N-terminus of delta-catenin. When delta-catenin-expressing epithelial cells are induced to scatter in response to hepatocyte growth factor (HGF), STI571 leads to the rapid redistribution of delta-catenin and changes in cellular morphology. We suggest that delta-catenin is a possible Abl substrate and acts downstream of Abl to orchestrate actin-based cellular morphogenesis.
δ-连环蛋白与黏附连接相关，并促进细胞形态发生（Lu等人，1999年）。在此我们表明，δ-连环蛋白在培养的海马神经元的生长锥中与肌动蛋白丝和Abl酪氨酸激酶共定位。诱导表达δ-连环蛋白的PC12细胞在神经生长因子（NGF）刺激下显示出加速的神经突延伸。Abl家族激酶抑制剂STI571进一步增强了这些刺激作用。使用免疫复合物测定法，δ-连环蛋白在体外是Abl的有效底物，并且细胞内大多数由Abl诱导的酪氨酸磷酸化存在于δ-连环蛋白的N端。当诱导表达δ-连环蛋白的上皮细胞响应肝细胞生长因子（HGF）而分散时，STI571导致δ-连环蛋白的快速重新分布和细胞形态的变化。我们认为，δ-连环蛋白可能是Abl的底物，并在Abl的下游起作用，以协调基于肌动蛋白的细胞形态发生。
