Affixin activates Rac1 via βPIX in C2C12 myoblast
Affixin activates Rac1 via βPIX in C2C12 myoblast
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DOI：
10.1016/j.febslet.2008.01.064
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发表时间：
2008-04-09
期刊：
影响因子：
3.5
通讯作者：
Hayashi, Yukiko K.
中科院分区：
文献类型：
--
作者：
Matsuda, Chie;Kameyama, Kimihiko;Hayashi, Yukiko K.
粘附素/β-细小蛋白（Affixin/beta-parvin）是在骨骼肌和心脏中高度表达的整合素连接激酶（ILK）结合粘着斑蛋白。为了阐明附着素在骨骼肌中的可能作用，我们建立了稳定表达T7标记的人附着素的C2 C12细胞系（C2 C12-附着素细胞）。外源性表达的附加素促进片状伪足形成，其中附加素、ILK α p21-活化激酶（PAK）-相互作用交换因子（PIX）和β PIX积累。通过免疫沉淀和pull down测定证实了affixin和β PIX的缔合。在C2 C12-affixin细胞中，观察到激活的Rac 1而不是Cdc 42的水平增加，缺乏鸟嘌呤核苷酸交换因子活性的突变体PPIX抑制了板状伪足的形成。这些结果表明，affixin参与重组肌膜下的细胞骨架肌动蛋白通过激活Rac 1通过在骨骼肌中的α和β PIXs。
Affixin/beta-parvin is an integrin-linked kinase (ILK)binding focal adhesion protein highly expressed in skeletal muscle and heart. To elucidate the possible role of affixin in skeletal muscle, we established stable C2C12 cell line expressing T7-tagged human affixin (C2C12-affixin cells). Exogenous expression of affixin promotes lamellipodium formation where affixin, ILK alpha p21-activated kinase (PAK)-interactive exchange factor (PIX) and beta PIX accumulate. The association of affixin and beta PIX was confirmed by immunoprecipitation and pull down assay. In C2C12-affixin cells, an increased level of activated Rac1 but not Cdc42 was observed, and mutant PPIX lacking guanine nucleotide exchange factor activity inhibited lamellipodium formation. These results suggest that affixin is involved in reorganization of subsarcolemmal cytoskeletal actin by activation of Rac1 through a and beta PIXs in skeletal muscle.