PKD1 induces p21waf1 and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2
PKD1 induces p21waf1 and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2
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DOI：
10.1016/s0092-8674(02)00716-x
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发表时间：
2002-04-19
期刊：
影响因子：
64.5
通讯作者：
Germino, GG
中科院分区：
文献类型：
--
作者：
Bhunia, AK;Piontek, K;Germino, GG
常染色体显性遗传性多囊肾病的特征是肾脏和其他器官中的囊肿形成，并由PKD 1或PKD 2突变引起。以前的研究表明，它们的基因产物在生长调节中具有重要作用。我们现在表明，多囊蛋白-1的表达激活JAK-STAT通路，从而上调p21（waf 1）和诱导细胞周期停滞在G 0/G1期。这一过程需要多囊蛋白-2，一种通道蛋白，作为一个重要的辅因子。破坏多囊蛋白-1/2结合的突变阻止该途径的激活。缺乏Pkd 1的小鼠胚胎具有缺陷的STAT 1磷酸化和p21（waf 1）诱导。这些结果表明，多囊蛋白-1/2复合物的功能之一是调节JAK/STAT途径，并解释了任一基因的突变如何导致生长失调。
Autosomal dominant polycystic kidney disease is characterized by cyst formation in the kidney and other organs and results from mutations of PKD1 or PKD2. Previous studies suggest that their gene products have an important role in growth regulation. We now show that expression of polycystin-1 activates the JAK-STAT pathway, thereby upregulating p21(waf1) and inducing cell cycle arrest in G0/G1. This process requires polycystin-2, a channel protein, as an essential cofactor. Mutations that disrupt polycystin-1/2 binding prevent activation of the pathway. Mouse embryos lacking Pkd1 have defective STAT1 phosphorylation and p21(waf1) induction. These results suggest that one function of the polycystin-1/2 complex is to regulate the JAK/STAT pathway and explain how mutations of either gene can result in dysregulated growth.