Nakanishi Hiroyuki, Takai Yoshimi
Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
J Cell Mol Med. 2008 Aug;12(4):1169-76. doi: 10.1111/j.1582-4934.2008.00345.x. Epub 2008 Apr 9.
Frabin, together with, at least, FGD1, FGD2, FGD3 and FGD1-related Cdc42-GEF (FRG), is a member of a family of Cdc42-specific gua-nine nucleotide exchange factors (GEFs). These proteins have multiple phosphoinositide-binding domains, including two pleckstrin homology (PH) domains and an FYVE or FERM domain. It is likely that they couple the actin cytoskeleton with the plasma membrane. Frabin associates with a specific actin structure(s) and induces the direct activation of Cdc42 in the vicinity of this structure(s), resulting in actin reorganization. Furthermore, frabin associates with a specific membrane structure(s) and induces the indirect activation of Rac in the vicinity of this structure(s), resulting in the reorganization of the actin cytoskeleton. This reorganization of the actin cytoskeleton induces cell shape changes such as the formation of filopodia and lamellipodia.
Frabin与至少FGD1、FGD2、FGD3以及与FGD1相关的Cdc42鸟嘌呤核苷酸交换因子(FRG)同属Cdc42特异性鸟嘌呤核苷酸交换因子(GEF)家族成员。这些蛋白质具有多个磷酸肌醇结合结构域,包括两个普列克底物蛋白同源(PH)结构域和一个FYVE或FERM结构域。它们可能将肌动蛋白细胞骨架与质膜连接起来。Frabin与特定的肌动蛋白结构结合,并在该结构附近诱导Cdc42的直接激活,从而导致肌动蛋白重组。此外,Frabin与特定的膜结构结合,并在该结构附近诱导Rac的间接激活,导致肌动蛋白细胞骨架的重组。这种肌动蛋白细胞骨架的重组会诱导细胞形态变化,如丝状伪足和片状伪足的形成。