Bhunia Anil Kumar, Piontek Klaus, Boletta Alessandra, Liu Lijuan, Qian Feng, Xu Pei Ning, Germino F Joseph, Germino Gregory G
Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell. 2002 Apr 19;109(2):157-68. doi: 10.1016/s0092-8674(02)00716-x.
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.
常染色体显性多囊肾病的特征是在肾脏和其他器官中形成囊肿，由PKD1或PKD2的突变引起。先前的研究表明，它们的基因产物在生长调节中起重要作用。我们现在表明，多囊蛋白-1的表达激活JAK-STAT途径，从而上调p21（waf1）并诱导细胞周期停滞在G0/G1期。这个过程需要多囊蛋白-2，一种通道蛋白，作为必需的辅助因子。破坏多囊蛋白-1/2结合的突变会阻止该途径的激活。缺乏Pkd1的小鼠胚胎具有STAT1磷酸化缺陷和p21（waf1）诱导缺陷。这些结果表明，多囊蛋白-1/2复合物的一个功能是调节JAK/STAT途径，并解释了任一基因的突变如何导致生长失调。
