Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3 complex and enhances actin polymerization by WASP
Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3 complex and enhances actin polymerization by WASP
复制标题
DOI：
10.1016/s1097-2765(03)00172-2
复制
发表时间：
2003-05-01
期刊：
影响因子：
16
通讯作者：
Ridley, AJ
中科院分区：
文献类型：
--
作者：
Cory, GOC;Cramer, R;Ridley, AJ
Wiskott-Aldrich综合征蛋白（WASP）和神经（N）-WASP通过其VCA结构域结合并刺激Arp 2/3复合物的肌动蛋白成核活性的能力来调节动态肌动蛋白结构。在这里，我们确定了两个磷酸化位点的VCA域的WASP在丝氨酸483和484。S483和S484是酪蛋白激酶2的体外和体内底物。这些残基的磷酸化使VCA结构域对Arp 2/3复合物的亲和力增加7倍，并且是全长WASP分子有效体外肌动蛋白聚合所需的。我们建议，组成VCA结构域磷酸化所需的Arp 2/3复合物的WASP的最佳刺激。
Wiskott-Aldrich syndrome protein (WASP) and neural (N)-WASP regulate dynamic actin structures through the ability of their VCA domains to bind to and stimulate the actin nucleating activity of the Arp2/3 complex. Here we identify two phosphorylation sites in the VCA domain of WASP at serines 483 and 484. S483 and S484 are substrates for casein kinase 2 in vitro and in vivo. Phosphorylation of these residues increases the affinity of the VCA domain for the Arp2/3 complex 7-fold and is required for efficient in vitro actin polymerization by the full-length WASP molecule. We propose that constitutive VCA domain phosphorylation is required for optimal stimulation of the Arp2/3 complex by WASP.