Gong J, Xu J, Bezanilla M, van Huizen R, Derin R, Li M
Department of Physiology, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Science. 1999 Sep 3;285(5433):1565-9. doi: 10.1126/science.285.5433.1565.
Targeting of protein modification enzymes is a key biochemical step to achieve specific and effective posttranslational modifications. Two alternatively spliced ZIP1 and ZIP2 proteins are described, which bind to both Kvbeta2 subunits of potassium channel and protein kinase C (PKC) zeta, thereby acting as a physical link in the assembly of PKCzeta-ZIP-potassium channel complexes. ZIP1 and ZIP2 differentially stimulate phosphorylation of Kvbeta2 by PKCzeta. They also interact to form heteromultimers, which allows for a hybrid stimulatory activity to PKCzeta. Finally, ZIP1 and ZIP2 coexist in the same cell type and are elevated differentially by neurotrophic factors. These results provide a mechanism for specificity and regulation of PKCzeta-targeted phosphorylation.
靶向蛋白质修饰酶是实现特异性和有效翻译后修饰的关键生化步骤。本文描述了两种选择性剪接的ZIP1和ZIP2蛋白，它们与钾通道的两个Kvbeta2亚基以及蛋白激酶C（PKC）ζ结合，从而在PKCζ-ZIP-钾通道复合物的组装中起到物理连接作用。ZIP1和ZIP2对PKCζ介导的Kvbeta2磷酸化具有不同的刺激作用。它们还相互作用形成异源多聚体，从而对PKCζ产生混合刺激活性。最后，ZIP1和ZIP2共存于同一细胞类型中，并被神经营养因子以不同方式上调。这些结果为PKCζ靶向磷酸化的特异性和调节提供了一种机制。
