ArticleThe Journal of clinical investigation2014
Integrin-mediated type II TGF-β receptor tyrosine dephosphorylation controls SMAD-dependent profibrotic signaling.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 74 citations in OpenAlex.
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- PTPN1/PTPN2 inhibition improves NK cancer therapy by enhancing IL-2 and mitigating TGFβ1 responses.EMBO reports · 2026Article
- Integrin α 1 β 1 Promotes Interstitial Fibrosis and Cyst Growth in a Mouse Model of Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2026Article
- ATF3 aggravates kidney fibrosis via HDAC6-dependent epigenetic reprogramming.International journal of biological sciences · 2026Article
- Role of the integrin‑β1/TGF‑β1 signaling pathway in the pathogenesis of pelvic organ prolapse: A study on vaginal wall tissue alterations and molecular dysfunction.Molecular medicine reports · 2025Article
- Integrins in the kidney - beyond the matrix.Nature reviews. Nephrology · 2025Review
- Decoding clinical diversity in monogenic TGFBR1 and TGFBR2 mutations: insights into the interplay of molecular mechanisms and hypomorphicity.Frontiers in cell and developmental biology · 2025Review
- Article
- TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review).Molecular medicine reports · 2024Review
- TGFβ Signaling Dysregulation May Contribute to COL4A1-Related Glaucomatous Optic Nerve Damage.Investigative ophthalmology & visual science · 2024Article
- Role of integrin β1 and tenascin C mediate TGF-SMAD2/3 signaling in chondrogenic differentiation of BMSCs induced by type I collagen hydrogel.Regenerative biomaterials · 2024Article
- Depleting transforming growth factor beta receptor 2 signalling in the cartilage ofOsteoarthritis and cartilage open · 2023Article
- Chondrocyte primary cilia lengthening and shortening in response to mediators of osteoarthritis; a role for integrin α1β1 and focal adhesions.Osteoarthritis and cartilage open · 2023Article
- Nanofiber-based glaucoma drainage implant improves surgical outcomes by modulating fibroblast behavior.Bioengineering & translational medicine · 2023Article
- Sexual dimorphism in reactive oxygen species production and a role for integrin α1β1 in estrogen receptor α and β expression in articular cartilage.Journal of orthopaedic surgery and research · 2023Article
- Elevated TGFβ signaling contributes to cerebral small vessel disease in mouse models of Gould syndrome.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Role of integrins in the development of fibrosis in the trabecular meshwork.Frontiers in ophthalmology · 2023Review
- Elevated TGFβ signaling contributes to ocular anterior segment dysgenesis in Col4a1 mutant mice.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- The catalytic activity of TCPTP is auto-regulated by its intrinsically disordered tail and activated by Integrin alpha-1.Nature communications · 2022Article
- Mechanosensitive Regulation of Fibrosis.Cells · 2021Review
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13 authors at 4 institutions in 3 countries.
Funding
Abstract
Tubulointerstitial fibrosis underlies all forms of end-stage kidney disease. TGF-β mediates both the development and the progression of kidney fibrosis through binding and activation of the serine/threonine kinase type II TGF-β receptor (TβRII), which in turn promotes a TβRI-mediated SMAD-dependent fibrotic signaling cascade. Autophosphorylation of serine residues within TβRII is considered the principal regulatory mechanism of TβRII-induced signaling; however, there are 5 tyrosine residues within the cytoplasmic tail that could potentially mediate TβRII-dependent SMAD activation. Here, we determined that phosphorylation of tyrosines within the TβRII tail was essential for SMAD-dependent fibrotic signaling within cells of the kidney collecting duct. Conversely, the T cell protein tyrosine phosphatase (TCPTP) dephosphorylated TβRII tail tyrosine residues, resulting in inhibition of TβR-dependent fibrotic signaling. The collagen-binding receptor integrin α1β1 was required for recruitment of TCPTP to the TβRII tail, as mice lacking this integrin exhibited impaired TCPTP-mediated tyrosine dephosphorylation of TβRII that led to severe fibrosis in a unilateral ureteral obstruction model of renal fibrosis. Together, these findings uncover a crosstalk between integrin α1β1 and TβRII that is essential for TβRII-mediated SMAD activation and fibrotic signaling pathways.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.