Yi Sun-Ju, Hwang Seong Yun, Oh Myung-Ju, Kim Kyunghwan, Jhun Byung H
School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, Republic of Korea.
Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, Republic of Korea.
Anim Cells Syst (Seoul). 2018 Mar 7;22(2):69-75. doi: 10.1080/19768354.2018.1447013. eCollection 2018.
p130 Crk-associated substrate (Cas) is an adaptor protein associating with many other signaling proteins and regulates a various biological processes including cell adhesion, migration, and growth factor stimulation. However, the exact functional role of Cas in growth factor signaling pathway was poorly understood. Here we investigated the role of Cas and its domains in the effects of insulin, EGF, and IGF-1 on c-Jun gene expression, DNA synthesis, cytoskeletal reorganization. We found that microinjection of anti-Cas antibody and C-terminal domain of Cas (Cas-CT) specifically inhibited EGF-induced, but not insulin- or IGF-1-induced, c-Jun expression. Cell cycle progression and cytoskeleton reorganization induced by insulin and EGF, but not by IGF-1, were inhibited by microinjected anti-Cas and Cas-CT. In contrast, microinjection of the substate domain (Cas-SD) of Cas did not have any inhibitory effects. These results revealed that the Cas-CT is differentially implicated in insulin and EGF-mediated, but not IGF-1-mediated, c-Jun expression, DNA synthesis and membrane ruffling.
p130 Crk相关底物（Cas）是一种衔接蛋白，可与许多其他信号蛋白结合，并调节包括细胞黏附、迁移和生长因子刺激在内的多种生物学过程。然而，Cas在生长因子信号通路中的确切功能作用尚不清楚。在此，我们研究了Cas及其结构域在胰岛素、表皮生长因子（EGF）和胰岛素样生长因子-1（IGF-1）对c-Jun基因表达、DNA合成、细胞骨架重组的影响中的作用。我们发现，显微注射抗Cas抗体和Cas的C末端结构域（Cas-CT）可特异性抑制EGF诱导的c-Jun表达，但不抑制胰岛素或IGF-1诱导的c-Jun表达。显微注射抗Cas和Cas-CT可抑制胰岛素和EGF诱导的细胞周期进程和细胞骨架重组，但不抑制IGF-1诱导的细胞周期进程和细胞骨架重组。相比之下，显微注射Cas的底物结构域（Cas-SD）没有任何抑制作用。这些结果表明，Cas-CT在胰岛素和EGF介导的c-Jun表达、DNA合成及膜皱襞形成中发挥不同作用，但在IGF-1介导的过程中并非如此。
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