Dap160/intersectin binds and activates aPKC to regulate cell polarity and cell cycle progression
Dap160/intersectin binds and activates aPKC to regulate cell polarity and cell cycle progression
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DOI：
10.1242/dev.024059
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发表时间：
2008-08-15
期刊：
影响因子：
4.6
通讯作者：
Doe, Chris Q.
中科院分区：
文献类型：
--
作者：
Chabu, Chiswili;Doe, Chris Q.
非典型蛋白激酶 C (aPKC) 是许多细胞类型的细胞极化所必需的，并且在多种人类肿瘤中表达上调。尽管 aPKC 在细胞极性和生长控制中很重要，但人们对 aPKC 活性如何调节的了解相对较少。在这里，我们使用生化方法将 Dynamin 相关蛋白 160（Dap160；与哺乳动物 intersectin 相关）鉴定为果蝇中的 aPKC 相互作用蛋白。我们发现 Dap160 直接与 aPKC 相互作用，在体外刺激 aPKC 活性，并与 aPKC 共定位于胚胎神经母细胞的顶皮层。在 dap160 突变体中，aPKC 从神经母细胞顶皮层离域，并且活性降低，因为它无法从基底皮层取代已知的靶蛋白。 dap160 和 aPKC 突变体都具有较少的增殖神经母细胞和延长的神经母细胞细胞周期。我们得出结论，Dap160 正向调节 aPKC 活性和定位，以促进神经母细胞极性和细胞周期进程。
The atypical protein kinase C (aPKC) is required for cell polarization of many cell types, and is upregulated in several human tumors. Despite its importance in cell polarity and growth control, relatively little is known about how aPKC activity is regulated. Here, we use a biochemical approach to identify Dynamin-associated protein 160 (Dap160; related to mammalian intersectin) as an aPKC-interacting protein in Drosophila. We show that Dap160 directly interacts with aPKC, stimulates aPKC activity in vitro and colocalizes with aPKC at the apical cortex of embryonic neuroblasts. In dap160 mutants, aPKC is delocalized from the neuroblast apical cortex and has reduced activity, based on its inability to displace known target proteins from the basal cortex. Both dap160 and aPKC mutants have fewer proliferating neuroblasts and a prolonged neuroblast cell cycle. We conclude that Dap160 positively regulates aPKC activity and localization to promote neuroblast cell polarity and cell cycle progression.