Arf GTP-binding proteins and membrane traffic

我们继续评估Arf 6和高尔基体相关的Arfs如Arf 1在质膜上所起的作用。 GTP结合蛋白如Arf在GTP结合的活性形式和GDP结合的非活性形式之间循环。我们已经发现，Arf 1，通常认为在高尔基复合体的功能，是必需的腹侧肌动蛋白结构形成佛波酯治疗。 佛波酯如PMA是肿瘤促进剂，并导致蛋白激酶C和Src家族激酶的活化。 这些腹侧肌动蛋白结构代表了皮质肌动蛋白细胞骨架和粘着斑的主要重组。 这增加了越来越多的细胞活动发生在质膜上，现在被认为涉及Arf 1。所有Arf蛋白共享共同的效应器（磷脂酶D和磷脂酰肌醇4-磷酸5-激酶的刺激），然而它们可以被不同的鸟嘌呤核苷酸交换因子（GEF）和GTP酶激活蛋白（GAP）激活。 此外，这些GEF和GAP本身可能具有独特的信号传导和支架功能，从而产生不同的信号传导输出。

We continue to evaluate the roles played by Arf6 and also Golgi-associated Arfs like Arf1 at the plasma membrane. GTP-binding proteins like Arf cycle between GTP-bound, active and GDP-bound, inactive forms. We have found that Arf1, typically thought to function at the Golgi complex, is required for ventral actin structures formed in response to phorbol ester treatment. Phorbol esters like PMA are tumor promoters and lead to the activation of protein kinase C and Src family kinases. These ventral actin structures represent a major re-organization of the cortical actin cytoskeleton and focal adhesions. This adds to the growing list of cellular activities occurring at the plasma membrane that now are thought to involve Arf1. All Arf protein share common effectors (stimulation of phospholipase D, and phosphatidylinositol 4-phosphate 5-kinase) however they may be activated by different guanine nucleotide exchange factors (GEFs) and GTP-ase activating proteins (GAPs). Furthermore these GEFs and GAPs themselves may have unique signaling and scaffolding functions giving rise to distinct signaling outputs.