Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2.
Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2.
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DOI：
10.1073/pnas.94.13.6965
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发表时间：
1997-06
影响因子：
11.1
通讯作者：
L. Tsiokas;E. Kim;T. Arnould;V. Sukhatme;G. Walz
中科院分区：
文献类型：
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作者：
L. Tsiokas;E. Kim;T. Arnould;V. Sukhatme;G. Walz
PKD1和PKD2是最近发现的两个基因，它们与绝大多数常染色体多囊肾病（一种导致进行性肾衰竭的常见遗传性疾病）有关。PKD1编码多囊蛋白，多囊蛋白是一种大糖蛋白，含有几种细胞外基序，表明在细胞-细胞或细胞-基质相互作用中起作用，PKD2编码一种与电压激活钙通道和PKD1同源的蛋白质。目前尚不清楚这两种蛋白的突变如何在功能上引起常染色体多囊肾病。我们发现PKD1和PKD2通过它们的c端细胞质尾部相互作用。这种相互作用导致PKD1而非PKD2的上调。此外，PKD2而不是PKD1的细胞质尾部通过不同于与PKD1相互作用所需区域的卷曲结构域形成同型二聚体。这些相互作用表明PKD1和PKD2可能通过一个共同的信号通路起作用，这是正常小管形成所必需的，PKD1可能需要PKD2的存在才能稳定表达。
PKD1 and PKD2 are two recently identified genes that are responsible for the vast majority of autosomal polycystic kidney disease, a common inherited disease that causes progressive renal failure. PKD1 encodes polycystin, a large glycoprotein that contains several extracellular motifs indicative of a role in cell-cell or cell-matrix interactions, and the PKD2 encodes a protein with homology to a voltage-activated calcium channel and to PKD1. It is currently unknown how mutations of either protein functionally cause autosomal polycystic kidney disease. We show that PKD1 and PKD2 interact through their C-terminal cytoplasmic tails. This interaction resulted in an up-regulation of PKD1 but not PKD2. Furthermore, the cytoplasmic tail of PKD2 but not PKD1 formed homodimers through a coiled-coil domain distinct from the region required for interaction with PKD1. These interactions suggest that PKD1 and PKD2 may function through a common signaling pathway that is necessary for normal tubulogenesis and that PKD1 may require the presence of PKD2 for stable expression.