PKD1 induces p21waf1 and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2

Anil Kumar Bhunia, Klaus Piontek, Alessandra Boletta, Lijuan Liu, Feng Qian, Pei Ning Xu, F. Joseph Germino, Gregory G. Germino

Research output: Contribution to journalArticle

Abstract

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 p21waf1 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 p21waf1 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.

Original languageEnglish (US)
Pages (from-to)157-168
Number of pages12
JournalCell
Volume109
Issue number2
DOIs
StatePublished - Apr 19 2002

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Bhunia, A. K., Piontek, K., Boletta, A., Liu, L., Qian, F., Xu, P. N., Germino, F. J., & Germino, G. G. (2002). PKD1 induces p21waf1 and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell, 109(2), 157-168. https://doi.org/10.1016/S0092-8674(02)00716-X