ArticleArthritis and rheumatism2011
The c-Abl tyrosine kinase controls protein kinase Cδ-induced Fli-1 phosphorylation in human dermal fibroblasts.
Article in Arthritis and rheumatism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 51 citations in OpenAlex.
- Fli1 represses transcription of the human α2(I) collagen gene by recruitment of the HDAC1/p300 complex.PloS one · 2013Trial
- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.Frontiers in dementia · 2024Review
- Fli1 and Tissue Fibrosis in Various Diseases.International journal of molecular sciences · 2023Review
- Perspective to precision medicine in scleroderma.Frontiers in immunology · 2023Article
- Myofibroblast specific targeting approaches to improve fibrosis treatment.Chemical communications (Cambridge, England) · 2022Review
- Candidate rejuvenating factor GDF11 and tissue fibrosis: friend or foe?GeroScience · 2020Review
- Molecular Signatures of Sinus Node Dysfunction Induce Structural Remodeling in the Right Atrial Tissue.Molecules and cells · 2020Article
- Active roles of dysfunctional vascular endothelium in fibrosis and cancer.Journal of biomedical science · 2019Review
- A cAbl-MRTF-A Feedback Loop Contributes to Hepatic Stellate Cell Activation.Frontiers in cell and developmental biology · 2019Article
- Role of the Fyn-PKCδ signaling in SE-induced neuroinflammation and epileptogenesis in experimental models of temporal lobe epilepsy.Neurobiology of disease · 2018Article
- Article
- Endothelin receptor blockade ameliorates vascular fragility in endothelial cell-specific Fli-1-knockout mice by increasing Fli-1 DNA binding ability.Arthritis & rheumatology (Hoboken, N.J.) · 2015Article
- Review
- Cellular mechanisms of tissue fibrosis. 8. Current and future drug targets in fibrosis: focus on Rho GTPase-regulated gene transcription.American journal of physiology. Cell physiology · 2014Review
- Oncogenic Fli-1 is a potential prognostic marker for the progression of epithelial ovarian cancer.BMC cancer · 2014Article
- Bosentan reverses the pro-fibrotic phenotype of systemic sclerosis dermal fibroblasts via increasing DNA binding ability of transcription factor Fli1.Arthritis research & therapy · 2014Article
- Animal models of scleroderma: current state and recent development.Current rheumatology reports · 2013Review
- Ciprofloxacin has antifibrotic effects in scleroderma fibroblasts via downregulation of Dnmt1 and upregulation of Fli1.International journal of molecular medicine · 2012Article
- Elevated expression of cav-1 in a subset of SSc fibroblasts contributes to constitutive Alk1/Smad1 activation.Journal of cellular and molecular medicine · 2012Article
- The Abl and Arg kinases mediate distinct modes of phagocytosis and are required for maximal Leishmania infection.Molecular and cellular biology · 2012Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveWe have previously demonstrated that in response to transforming growth factor β (TGFβ), Fli-1 activity is repressed through a series of sequential posttranslational modifications, consisting of protein kinase Cδ (PKCδ)-induced Thr312 phosphorylation, acetylation by p300/CREB binding protein-associated factor, and detachment from the collagen promoter. The purpose of this study was to further investigate the upstream events that lead to Fli-1 phosphorylation in response to TGFβ.
methodsDermal fibroblasts were isolated from systemic sclerosis (SSc) patients and healthy control subjects matched for age, sex, and ethnicity. Western blotting was used to analyze protein levels and real-time quantitative reverse transcription-polymerase chain reaction analysis was used to measure messenger RNA expression. Cells were transduced with constitutively active PKCδ adenovirus or were transiently transfected with a Bcr-Abl-overexpressing plasmid. Subcellular localization of PKCδ was examined by immunocytochemistry.
resultsWestern blot analysis of cell lysates demonstrated that the levels of phospho-Fli-1 (Thr312) were up-regulated in SSc fibroblasts, correlating with increased levels of type I collagen and c-Abl protein. Experiments using a constitutively activated form of c-Abl, small interfering RNA against c-Abl and the specific tyrosine kinase inhibitor imatinib, demonstrated the requirement of c-Abl for the TGFβ-induced phosphorylation of Fli-1. Additionally, we showed that c-Abl kinase activity was required for nuclear localization of PKCδ.
conclusionOur results demonstrate that in SSc fibroblasts, c-Abl is an upstream regulator of the profibrotic PKCδ/phospho-Fli-1 pathway, via induction of PKCδ nuclear localization. Additionally, the finding that Fli-1 is phosphorylated at higher levels in SSc fibroblasts supports the notion that the c-Abl/PKCδ/phospho-Fli-1 pathway is constitutively activated in these cells. Thus, blocking the TGFβ/c-Abl/PKCδ/phospho-Fli-1 pathway could be an attractive alternative approach to therapy for scleroderma.
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