Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2
Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2
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DOI：
10.1074/jbc.m008932200
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发表时间：
2001-03-16
影响因子：
4.8
通讯作者：
De Camilli, P
中科院分区：
文献类型：
--
作者：
Floyd, SR;Porro, EB;De Camilli, P
Amphiphyn 1 是一种在神经元中高水平表达的磷蛋白，参与突触小泡内吞作用和神经突生长。它是细胞周期蛋白依赖性激酶 (cdk) 5 的底物，细胞周期蛋白依赖性激酶 (cdk) 5 是细胞周期蛋白依赖性蛋白激酶家族的成员，通过其对肌动蛋白细胞骨架的作用，在功能上与神经元迁移和神经突生长相关。两栖蛋白的酵母同源物 Rvs167 在内吞作用和肌动蛋白动力学中发挥作用，被 cdk5 同源物 Pho85 磷酸化，并结合 Pho85 调节亚基 Pcl2。我们在此表明两栖蛋白 1 与 cdk5 激活亚基 p35 相互作用，并且这种相互作用是由两栖蛋白的保守 NH2 末端区域介导的，两栖蛋白 I 共定位p35 存在于神经元的生长锥中以及转染的成纤维细胞中富含肌动蛋白的外周板状伪足中。 Amphiphyn 在包括丝氨酸 272、276 和 285 的区域被 cdk5 磷酸化，Amphiphyn I 也被同一区域的 cdc2/cyclin B 激酶复合物磷酸化，并在分裂细胞中经历有丝分裂磷酸化。这些数据表明，细胞周期蛋白依赖性激酶家族成员的磷酸化是 Amphiphyn 的保守特性，并表明这种磷酸化可能发挥重要作用。在有丝分裂和分化细胞中的生理作用。
Amphiphysin 1 is a phosphoprotein expressed at high levels in neurons, where it participates in synaptic vesicle endocytosis and neurite outgrowth. It is a substrate for cyclin-dependent kinase (cdk) 5, a member of the cyclin-dependent protein kinase family, which has been functionally linked to neuronal migration and neurite outgrowth via its action on the actin cytoskeleton. The yeast homologue of amphiphysin, Rvs167, functions in endocytosis and actin dynamics, is phosphorylated by the cdk5 homologue Pho85, and binds the Pho85 regulatory subunit Pcl2, We show here that amphiphysin 1 interacts with the cdk5-activating subunit p35 and that this interaction is mediated by the conserved NH2-terminal region of amphiphysin, Amphiphysin I colocalizes with p35 in the growth cones of neurons and at actin-rich peripheral lamellipodia in transfected fibroblasts. Amphiphysin is phosphorylated by cdk5 in a region including serines 272, 276, and 285, Amphiphysin I is also phosphorylated by the cdc2/cyclin B kinase complex in the same region and undergoes mitotic phosphorylation in dividing cells, These data indicate that phosphorylation by members of the cyclin-dependent kinase family is a conserved property of amphiphysin and suggest that this phosphorylation may play an important physioiogical role both in mitosis and in differentiated cells.