PKD1 Induces p21waf1 and Regulation of the Cell Cycle via Direct Activation of the JAK-STAT Signaling Pathway in a Process Requiring PKD2
Copyright policy )PKD1 Induces p21waf1 and Regulation of the Cell Cycle via Direct Activation of the JAK-STAT Signaling Pathway in a Process Requiring PKD2
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.
- JOHNS HOPKINS UNIVERSITY
- University of Medicine and Dentistry of New Jersey United States
- Johns Hopkins Medicine United States
- Johns Hopkins University School of Medicine United States
Cyclin-Dependent Kinase Inhibitor p21, Male, Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Cell Cycle, G1 Phase, Membrane Proteins, Proteins, Janus Kinase 2, Protein-Tyrosine Kinases, Polycystic Kidney, Autosomal Dominant, Resting Phase, Cell Cycle, DNA-Binding Proteins, Mice, Cyclins, Proto-Oncogene Proteins, Mutation, Animals, Humans, Female, Cell Division
Cyclin-Dependent Kinase Inhibitor p21, Male, Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Cell Cycle, G1 Phase, Membrane Proteins, Proteins, Janus Kinase 2, Protein-Tyrosine Kinases, Polycystic Kidney, Autosomal Dominant, Resting Phase, Cell Cycle, DNA-Binding Proteins, Mice, Cyclins, Proto-Oncogene Proteins, Mutation, Animals, Humans, Female, Cell Division
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