ArticleJournal of the American Society of Nephrology : JASN2014
The cleaved cytoplasmic tail of polycystin-1 regulates Src-dependent STAT3 activation.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- The Role of Immune Cells as Modulators of Progression in Polycystic Kidney Disease: A Systematic Review.Kidney360 · 2026Pooled it
- Polycystin-1 and Cardiac Remodeling: From Mechanotransduction to Clinical Consequences.Circulation research · 2026Review
- Discovery of a potent STAT3 inhibitor WR-S-647 for the treatment of ADPKD.Archives of pharmacal research · 2026Article
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Phosphoproteomic response to epidermal growth factor in native rat inner medullary collecting duct.American journal of physiology. Renal physiology · 2025Article
- Defects of renal tubular homeostasis and cystogenesis in theiScience · 2024Article
- Ttc21b deficiency attenuates autosomal dominant polycystic kidney disease in a kidney tubular- and maturation-dependent manner.Kidney international · 2022Article
- Restoration of atypical protein kinase C ζ function in autosomal dominant polycystic kidney disease ameliorates disease progression.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- The Interaction Between Autophagy and JAK/STAT3 Signaling Pathway in Tumors.Frontiers in genetics · 2022Review
- Review
- Molecular Pathophysiology of Autosomal Recessive Polycystic Kidney Disease.International journal of molecular sciences · 2021Review
- Gene deficiency or pharmacological inhibition of PDCD4-mediated FGR signaling protects against acute kidney injury.Acta pharmaceutica Sinica. B · 2021Article
- Is There a Functional Role of Mitochondrial Dysfunction in the Pathogenesis of ARPKD?Frontiers in medicine · 2021Article
- Adhesion GPCRs as a paradigm for understanding polycystin-1 G protein regulation.Cellular signalling · 2020Review
- A cut above (and below): Protein cleavage in the regulation of polycystin trafficking and signaling.Cellular signalling · 2020Review
- STAT signaling in polycystic kidney disease.Cellular signalling · 2020Review
- Tubular STAT3 Limits Renal Inflammation in Autosomal Dominant Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2020Article
- SNX10 (sorting nexin 10) inhibits colorectal cancer initiation and progression by controlling autophagic degradation of SRC.Autophagy · 2020Article
- Interferon Regulatory Factor-5 in Resident Macrophage Promotes Polycystic Kidney Disease.Kidney360 · 2020Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Polycystin-1 (PC1) mutations result in proliferative renal cyst growth and progression to renal failure in autosomal dominant polycystic kidney disease (ADPKD). The transcription factor STAT3 (signal transducer and activator of transcription 3) was shown to be activated in cyst-lining cells in ADPKD and PKD mouse models and may drive renal cyst growth, but the mechanisms leading to persistent STAT3 activation are unknown. A proteolytic fragment of PC1 corresponding to the cytoplasmic tail, PC1-p30, is overexpressed in ADPKD. Here, we show that PC1-p30 interacts with the nonreceptor tyrosine kinase Src, resulting in Src-dependent activation of STAT3 by tyrosine phosphorylation. The PC1-p30-mediated activation of Src/STAT3 was independent of JAK family kinases and insensitive to the STAT3 inhibitor suppressor of cytokine signaling 3. Signaling by the EGF receptor (EGFR) or cAMP amplified the activation of Src/STAT3 by PC1-p30. Expression of PC1-p30 changed the cellular response to cAMP signaling. In the absence of PC1-p30, cAMP dampened EGFR- or IL-6-dependent activation of STAT3; in the presence of PC1-p30, cAMP amplified Src-dependent activation of STAT3. In the polycystic kidney (PCK) rat model, activation of STAT3 in renal cystic cells depended on vasopressin receptor 2 (V2R) signaling, which increased cAMP levels. Genetic inhibition of vasopressin expression or treatment with a pharmacologic V2R inhibitor strongly suppressed STAT3 activation and reduced renal cyst growth. These results suggest that PC1, via its cleaved cytoplasmic tail, integrates signaling inputs from EGFR and cAMP, resulting in Src-dependent activation of STAT3 and a proliferative response.
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