Umikawa M, Obaishi H, Nakanishi H, Satoh-Horikawa K, Takahashi K, Hotta I, Matsuura Y, Takai Y
Department of Molecular Biology and Biochemistry, Osaka University Medical School, Suita 565-0871, Japan.
J Biol Chem. 1999 Sep 3;274(36):25197-200. doi: 10.1074/jbc.274.36.25197.
We have recently isolated a novel actin filament-binding protein, named frabin. Frabin has one actin filament-binding domain (ABD), one Dbl homology domain (DHD), first pleckstrin homology domains (PHD) adjacent to DHD, one cysteine rich-domain (CRD), and second PHD from the N terminus to the C terminus in this order. Full-length frabin induces microspike formation and c-Jun N-terminal kinase (JNK) activation. We found here that the fragment of frabin containing DHD and first PHD stimulated guanine nucleotide exchange of Cdc42Hs small G protein, but not that of RhoA or Rac1 small G protein. However, this fragment of frabin did not induce microspike formation, and ABD was additionally necessary for microspike formation. Frabin having ABD was associated with the actin cytoskeleton, whereas frabin lacking ABD was diffusely distributed in the cytoplasm. In contrast, ABD was not necessary for JNK activation but CRD and second PHD were additionally necessary for this activation. These results indicate that the association of frabin with the actin cytoskeleton is essential for microspike formation but not for JNK activation and that different domains of frabin are involved in microspike formation and JNK activation through Cdc42 activation.
我们最近分离出一种名为frabin的新型肌动蛋白丝结合蛋白。Frabin从N端到C端依次有一个肌动蛋白丝结合结构域（ABD）、一个双鸟苷酸交换因子同源结构域（DHD）、与DHD相邻的第一个普列克底物蛋白同源结构域（PHD）、一个富含半胱氨酸的结构域（CRD）和第二个PHD。全长frabin可诱导微刺形成和c-Jun氨基末端激酶（JNK）激活。我们在此发现，包含DHD和第一个PHD的frabin片段可刺激Cdc42Hs小G蛋白的鸟嘌呤核苷酸交换，但不能刺激RhoA或Rac1小G蛋白的鸟嘌呤核苷酸交换。然而，frabin的该片段不能诱导微刺形成，微刺形成还需要ABD。具有ABD的frabin与肌动蛋白细胞骨架相关，而缺乏ABD的frabin则在细胞质中呈弥散分布。相反，ABD对于JNK激活并非必需，但CRD和第二个PHD对于该激活是额外必需的。这些结果表明，frabin与肌动蛋白细胞骨架的结合对于微刺形成至关重要，但对于JNK激活并非如此，并且frabin的不同结构域通过Cdc42激活参与微刺形成和JNK激活。
