Recycling of Furin from the Plasma Membrane

Recycling of Furin from the Plasma Membrane
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从质膜中回收弗林蛋白酶

DOI:
--
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发表时间:
1999
影响因子:
4.8
通讯作者:
W. Garten
W. Garten
中科院分区:
生物学2区
文献类型:
--
作者:
M. Teuchert;S. Berghöfer;H. Klenk;W. Garten

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真核枯草杆菌蛋白酶样弗林蛋白酶在细胞内的主要定位是反式高尔基体网络(TGN),但也有一小部分位于细胞表面。细胞表面的弗林蛋白酶被内化并输送至 TGN。弗林蛋白酶胞质结构域中三个内吞作用基序的鉴定,即酪氨酸 (YKGL765) 基序、亮氨酸-异亮氨酸 (LI760) 基序和苯丙氨酸 (Phe790) 信号,表明弗林蛋白酶的内吞作用是通过 AP-2/网格蛋白依赖性途径发生的。由于人们对细胞质结构域中含有多种分选成分的蛋白质知之甚少,弗林蛋白酶尾中不同内化信号的组合提出了它们各自作用的问题。在这里,我们提供的数据显示弗林尾与 AP-2 质膜特异性接头复合物的介质 (μ2) 亚基在体外相互作用,并且这种相互作用主要取决于对基于酪氨酸的分选信号的识别,并在较小程度上取决于亮氨酸-异亮氨酸基序。我们进一步提供的证据表明,三种内吞信号对于体内弗林蛋白酶内化和 TGN 恢复具有不同的功能重要性,其中基于酪氨酸的基序是主要决定因素,其次是苯丙氨酸信号,而亮氨酸-异亮氨酸基序只是次要组成部分。最后,我们报道酪蛋白激酶 II 对弗林尾部的磷酸化不仅对于与 μ2 的有效相互作用和质膜的内化很重要,而且还决定了蛋白质从质膜到 TGN 的快速检索。
The predominant intracellular localization of the eukaryotic subtilisin-like endoprotease furin is the trans-Golgi network (TGN), but a small fraction is also found on the cell surface. Furin on the cell surface is internalized and delivered to the TGN. The identification of three endocytosis motifs, a tyrosine (YKGL765) motif, a leucine-isoleucine (LI760) motif, and a phenylalanine (Phe790) signal, in the furin cytoplasmic domain suggested that endocytosis of furin occurs via an AP-2/clathrin-dependent pathway. Since little is known about proteins containing multiple sorting components in their cytoplasmic domain, the combination of diverse internalization signals in the furin tail raised the question of their individual role. Here we present data showing that the furin tail interacts with the medium (μ2) subunit of the AP-2 plasma membrane-specific adaptor complex in vitro and that this interaction primarily depends on recognition of the tyrosine-based sorting signal and to less extent on the leucine-isoleucine motif. We further provide evidence that the three endocytosis signals are of different functional importance for furin internalization and retrieval to the TGN in vivo, with the tyrosine-based motif being the major determinant, followed by the phenylalanine signal, whereas the leucine-isoleucine motif is only a minor component. Finally, we report that phosphorylation of the furin tail by casein kinase II is not only important for efficient interaction with μ2 and internalization from the plasma membrane but also determines fast retrieval of the protein from the plasma membrane to the TGN.
DOI: 10.1002/j.1460-2075.1994.tb06231.x
发表时间: 1994-01-01
期刊: EMBO JOURNAL
影响因子: 11.4
作者:
MOLLOY, SS;THOMAS, L;THOMAS, G
通讯作者: THOMAS, G
DOI: 10.1093/nar/16.15.7351
发表时间: 1988-08-11
影响因子: 14.9
作者:
HIGUCHI, R;KRUMMEL, B;SAIKI, RK
通讯作者: SAIKI, RK
在培养的人体细胞中将表面甘露糖 6-磷酸受体转运至高尔基复合体。
DOI: --
发表时间: 1989
期刊: The Journal of biological chemistry
影响因子: --
作者:
Jin,M;SahagianJr,GG;Snider,MD
通讯作者: Snider,MD