Cory Giles O C, Cramer Rainer, Blanchoin Laurent, Ridley Anne J
Ludwig Institute for Cancer Research, Royal Free and University College Medical School Branch, Courtauld Building, 91 Riding House Street, London W1W 7BS, United Kingdom.
Mol Cell. 2003 May;11(5):1229-39. doi: 10.1016/s1097-2765(03)00172-2.
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.
威斯科特-奥尔德里奇综合征蛋白（WASP）和神经型（N）-WASP通过其VCA结构域结合并刺激Arp2/3复合体肌动蛋白成核活性的能力来调节动态肌动蛋白结构。在此，我们鉴定出WASP的VCA结构域中丝氨酸483和484处的两个磷酸化位点。在体外和体内，S483和S484都是酪蛋白激酶2的底物。这些残基的磷酸化使VCA结构域与Arp2/3复合体的亲和力增加7倍，并且是全长WASP分子在体外有效进行肌动蛋白聚合所必需的。我们提出，WASP对Arp2/3复合体的最佳刺激需要VCA结构域的组成型磷酸化。
