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粘菌盘基网柄菌磷酸酶 PP2A 的调节亚基 phr2AB 与中心体蛋白 CEP161 相互作用,CEP161 是 CDK5RAP2 的同源物。

The regulatory subunit phr2AB of Dictyostelium discoideum phosphatase PP2A interacts with the centrosomal protein CEP161, a CDK5RAP2 ortholog.

机构信息

Institute for Biochemistry I, Medical Faculty, University Hospital Cologne, Cologne, Germany.

Center for Molecular Medicine Cologne and Cologne Cluster on Cellular Stress Responses in Aging-Associated Diseases, Medical Faculty, University of Cologne, Cologne, Germany.

出版信息

Genes Cells. 2018 Oct;23(10):923-931. doi: 10.1111/gtc.12637. Epub 2018 Sep 21.

Abstract

phr2AB is the regulatory subunit of the Dictyostelium discoideum phosphatase PP2A and is the ortholog of the human B55 regulatory subunit of PP2A. phr2AB was isolated as a binding partner of the centrosomal protein CEP161, an ortholog of mammalian CDK5RAP2. CEP161 is presumably a phosphoprotein and a component of the Hippo pathway. The interaction site was located in the N-terminal half of CEP161 which encompasses the γTURC binding domain in CEP161. This binding domain is responsible for binding of the γ-tubulin ring complex which allows microtubule nucleation at the centrosome. GFP-tagged phr2AB is diffusely distributed throughout the cell and enriched at the centrosome. Ectopic expression of phr2AB as GFP fusion protein led to multinucleation, aberrant nucleus centrosome ratios and an altered sensitivity to okadaic acid. Some of these features were also affected in cells over-expressing domains of CEP161 and in cells from patients suffering from primary microcephaly, which carried a mutated CDK5RAP2 gene.

摘要

phr2AB 是盘基网柄菌磷酸酯酶 PP2A 的调节亚基,也是人 PP2A 的 B55 调节亚基的同源物。phr2AB 作为中心体蛋白 CEP161 的结合伴侣被分离出来,CEP161 是哺乳动物 CDK5RAP2 的同源物。CEP161 可能是一种磷酸化蛋白,是 Hippo 通路的一个组成部分。相互作用位点位于 CEP161 的 N 端,包含 CEP161 中的 γTURC 结合结构域。该结合结构域负责结合 γ-微管蛋白环复合物,从而允许微管在中心体处起始。GFP 标记的 phr2AB 在整个细胞中弥散分布,并在中心体处富集。GFP 融合蛋白过表达 phr2AB 会导致多核化、核中心体比例异常以及对 okadaic 酸的敏感性改变。这些特征中的一些也会受到 CEP161 结构域过表达的细胞以及患有原发性小头畸形的患者的细胞的影响,这些患者携带突变的 CDK5RAP2 基因。

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