ArticleHuman molecular genetics2013
Hyperphosphorylation of polycystin-2 at a critical residue in disease reveals an essential role for polycystin-1-regulated dephosphorylation.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- An integrin beta-1-anchored bicaudal C1-polycystin-1 module essential for tubular morphogenesis in polycystic kidney disease.iScience · 2026Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
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- Article
- Polycystin-1 regulates ARHGAP35-dependent centrosomal RhoA activation and ROCK signaling.JCI insight · 2020Article
- Polycystins as components of large multiprotein complexes of polycystin interactors.Cellular signalling · 2020Review
- An Overview of In Vivo and In Vitro Models for Autosomal Dominant Polycystic Kidney Disease: A Journey from 3D-Cysts to Mini-Pigs.International journal of molecular sciences · 2020Review
- Polycystin 2: A calcium channel, channel partner, and regulator of calcium homeostasis in ADPKD.Cellular signalling · 2020Review
- A high throughput zebrafish chemical screen reveals ALK5 and non-canonical androgen signalling as modulators of the pkd2Scientific reports · 2020Article
- Protein phosphatase 1α interacts with a novel ciliary targeting sequence of polycystin-1 and regulates polycystin-1 trafficking.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Polycystic kidney disease.Nature reviews. Disease primers · 2018Review
- A mutation affecting polycystin-1 mediated heterotrimeric G-protein signaling causes PKD.Human molecular genetics · 2018Article
- Expanding the role of vasopressin antagonism in polycystic kidney diseases: From adults to children?Pediatric nephrology (Berlin, Germany) · 2018Review
- Identification of clustered phosphorylation sites in PKD2L1: how PKD2L1 channel activation is regulated by cyclic adenosine monophosphate signaling pathway.Pflugers Archiv : European journal of physiology · 2018Article
- Ciliary Mechanisms of Cyst Formation in Polycystic Kidney Disease.Cold Spring Harbor perspectives in biology · 2017Review
- The Sorting Nexin 3 Retromer Pathway Regulates the Cell Surface Localization and Activity of a Wnt-Activated Polycystin Channel Complex.Journal of the American Society of Nephrology : JASN · 2017Article
- Polycystin-1 inhibits eIF2α phosphorylation and cell apoptosis through a PKR-eIF2α pathway.Scientific reports · 2017Article
- New Insights into the Molecular Mechanisms Targeting Tubular Channels/Transporters in PKD Development.Kidney diseases (Basel, Switzerland) · 2016Review
- Structural studies of the C-terminal tail of polycystin-2 (PC2) reveal insights into the mechanisms used for the functional regulation of PC2.The Journal of physiology · 2016Review
- The Polycystin-1, Lipoxygenase, and α-Toxin Domain Regulates Polycystin-1 Trafficking.Journal of the American Society of Nephrology : JASN · 2016Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Mutations in PKD1 (85%) or PKD2 (15%) account for almost all cases of autosomal dominant polycystic kidney disease (ADPKD). The ADPKD proteins, termed as polycystin-1 (PC1) and polycystin-2 (PC2), interact via their C-termini to form a receptor-ion channel complex whose function and regulation are not fully understood. Here, we report the first phosphorylated residue (Ser(829)) in PC2, whose dephosphorylation is mediated by PC1 binding through the recruitment of protein phosphatase-1 alpha (PP1α). Using a new phosphospecific antibody (pPC2) to this site, we demonstrate that Ser(829) is phosphorylated by Protein kinase A (PKA) but remains constitutively phosphorylated in cells and tissues lacking PC1. cAMP increased pSer(829) basolateral localization in MDCK cells in a time dependent manner and was essential for pronephric development in Xenopus embryos. When constitutively expressed, a complex phenotype associated with enhanced ATP-dependent ER Ca(2+) release and loss of growth suppression was observed in cycling cells. These results reveal a reciprocal functional link between PC1 and PC2 which is critically dependent on their interaction. Unopposed cAMP stimulated hyperphosphorylation of PC2 in the absence of functional PC1 could contribute to cyst initiation in PKD1 patients and represents a new molecular paradigm in understanding ADPKD pathogenesis.
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