ArticleMolecular and cellular biology2005
PKD2 functions as an epidermal growth factor-activated plasma membrane channel.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 174 citations in OpenAlex.
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- Cleavage of N-terminus of polycystin-1 increases calcium permeability of polycystin-1/2 receptor channel complexes.JCI insight · 2025Article
- FGFR2 residence in primary cilia is necessary for epithelial cell signaling.The Journal of cell biology · 2025Article
- Primary cilia and cancer: a tale of many faces.Oncogene · 2025Review
- Identification of polycystin 2 missense mutants targeted for endoplasmic reticulum-associated degradation.American journal of physiology. Cell physiology · 2025Article
- Polycystin-2 Mediated Calcium Signalling in theCells · 2024Article
- TRPP2 is located in the primary cilia of human non-pigmented ciliary epithelial cells.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Article
- Primary cilia-associated signalling in squamous cell carcinoma of head and neck region.Frontiers in oncology · 2024Review
- Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System.International journal of molecular sciences · 2023Review
- Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets.Frontiers in molecular biosciences · 2023Review
- Establishment of transgenic pigs overexpressing humanFrontiers in genetics · 2022Article
- Role of PKD2 in the endoplasmic reticulum calcium homeostasis.Frontiers in physiology · 2022Review
- Inward CaAmerican journal of physiology. Renal physiology · 2021Article
- Functional aspects of primary cilium in signaling, assembly and microenvironment in cancer.Journal of cellular physiology · 2021Review
- Species-Specific Regulation of TRPM2 by PI(4,5)PInternational journal of molecular sciences · 2021Article
- Primary Cilia-Related Pathways Moderate the Development and Therapy Resistance of Glioblastoma.Frontiers in oncology · 2021Review
- Autosomal dominant polycystic kidney disease and pioglitazone for its therapy: a comprehensive review with an emphasis on the molecular pathogenesis and pharmacological aspects.Molecular medicine (Cambridge, Mass.) · 2020Review
- Adaptive selection drives TRPP3 loss-of-function in an Ethiopian population.Scientific reports · 2020Article
- PIPProceedings of the National Academy of Sciences of the United States of America · 2020Review
- Polycystins as components of large multiprotein complexes of polycystin interactors.Cellular signalling · 2020Review
38 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
PKD2, or polycystin 2, the product of the gene mutated in type 2 autosomal dominant polycystic kidney disease, belongs to the transient receptor potential channel superfamily and has been shown to function as a nonselective cation channel in the plasma membrane. However, the mechanism of PKD2 activation remains elusive. We show that PKD2 overexpression increases epidermal growth factor (EGF)-induced inward currents in LLC-PK(1) kidney epithelial cells, while the knockdown of endogenous PKD2 by RNA interference or the expression of a pathogenic missense variant, PKD2-D511V, blunts the EGF-induced response. Pharmacological experiments indicate that the EGF-induced activation of PKD2 occurs independently of store depletion but requires the activity of phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K). Pipette infusion of purified phosphatidylinositol-4,5-bisphosphate (PIP(2)) suppresses the PKD2-mediated effect on EGF-induced conductance, while pipette infusion of phosphatidylinositol-3,4,5-trisphosphate (PIP(3)) does not have any effect on this conductance. Overexpression of type Ialpha phosphatidylinositol-4-phosphate 5-kinase [PIP(5)Kalpha], which catalyzes the formation of PIP(2), suppresses EGF-induced currents. Biochemical experiments show that PKD2 physically interacts with PLC-gamma2 and EGF receptor (EGFR) in transfected HEK293T cells and colocalizes with EGFR and PIP(2) in the primary cilium of LLC-PK(1) cells. We propose that plasma membrane PKD2 is under negative regulation by PIP(2). EGF may reduce the threshold of PKD2 activation by mechanical and other stimuli by releasing it from PIP(2)-mediated inhibition.
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