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含犰狳重复序列8α与肝细胞生长因子调节的酪氨酸激酶底物结合并促进其与泛素化蛋白的相互作用

Armadillo Repeat Containing 8alpha Binds to HRS and Promotes HRS Interaction with Ubiquitinated Proteins.

作者信息

Tomaru Koji, Ueda Atsuhisa, Suzuki Takeyuki, Kobayashi Nobuaki, Yang Jun, Yamamoto Masaki, Takeno Mitsuhiro, Kaneko Takeshi, Ishigatsubo Yoshiaki

机构信息

Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.

出版信息

Open Biochem J. 2010 Jan 13;4:1-8. doi: 10.2174/1874091X01004010001.

Abstract

Recently, we reported that a complex with an essential role in the degradation of Fructose-1,6-bisphosphatase in yeast is well conserved in mammalian cells; we named this mammalian complex C-terminal to the Lissencephaly type-1-like homology (CTLH) complex. Although the function of the CTLH complex remains unclear, here we used yeast two-hybrid screening to isolate Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) as a protein binding to a key component of CTLH complex, Armadillo repeat containing 8 (ARMc8) alpha. The association was confirmed by a yeast two-hybrid assay and a co-immunoprecipitation assay. The proline-rich domain of HRS was essential for the association. As demonstrated through immunofluorescence microscopy, ARMc8alpha co-localized with HRS. ARMc8alpha promoted the interaction of HRS with various ubiquitinated proteins through the ubiquitin-interacting motif. These findings suggest that HRS mediates protein endosomal trafficking partly through its interaction with ARMc8alpha.

摘要

最近,我们报道了一种在酵母中对果糖-1,6-二磷酸酶降解起关键作用的复合物在哺乳动物细胞中高度保守;我们将这种哺乳动物复合物命名为1型无脑回样同源结构域C端(CTLH)复合物。尽管CTLH复合物的功能仍不清楚,但在此我们利用酵母双杂交筛选分离出肝细胞生长因子调节的酪氨酸激酶底物(HRS),它是一种与CTLH复合物的关键组分含犰狳重复序列8(ARMc8)α结合的蛋白质。这种关联通过酵母双杂交试验和免疫共沉淀试验得以证实。HRS富含脯氨酸的结构域对这种关联至关重要。通过免疫荧光显微镜观察发现,ARMc8α与HRS共定位。ARMc8α通过泛素相互作用基序促进HRS与各种泛素化蛋白的相互作用。这些发现表明,HRS部分通过与ARMc8α的相互作用介导蛋白质的内体运输。

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