ArticleThe Journal of biological chemistry2014
IκB kinase γ/nuclear factor-κB-essential modulator (IKKγ/NEMO) facilitates RhoA GTPase activation, which, in turn, activates Rho-associated KINASE (ROCK) to phosphorylate IKKβ in response to transforming growth factor (TGF)-β1.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- Lysophosphatidic acid-mediated NF-κB activation promotes FOXC2 expression essential for lymphatic valve development.The Journal of clinical investigation · 2026Article
- NF-κB signaling as a critical inflammatory node in pulmonary arterial hypertension: from vascular remodeling to right heart failure.Frontiers in immunology · 2026Review
- Function of eEF-1γ in the nucleus in response to insulin in hepatocellular carcinoma cells.Communications biology · 2025Article
- Review
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- The Complex of p-Tyr42 RhoA and p-p65/RelA in Response to LPS Regulates the Expression of Phosphoglycerate Kinase 1.Antioxidants (Basel, Switzerland) · 2023Article
- Article
- Association of Phosphorylated Pyruvate Dehydrogenase with Pyruvate Kinase M2 Promotes PKM2 Stability in Response to Insulin.International journal of molecular sciences · 2023Article
- RhoA Signaling in Neurodegenerative Diseases.Cells · 2022Review
- Statins change the cytokine profile inFrontiers in immunology · 2022Article
- RhoA: a dubious molecule in cardiac pathophysiology.Journal of biomedical science · 2021Review
- TGF-β Pathway in Salivary Gland Fibrosis.International journal of molecular sciences · 2020Review
- ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism.Nature cell biology · 2020Article
- Regulation of RhoA GTPase and novel target proteins for ROCK.Small GTPases · 2020Review
- Rap1 regulates hepatic stellate cell migration through the modulation of RhoA activity in response to TGF‑β1.International journal of molecular medicine · 2019Article
- Microbial recognition by GEF-H1 controls IKKε mediated activation of IRF5.Nature communications · 2019Article
- Application of Proteomics to Inflammatory Bowel Disease Research: Current Status and Future Perspectives.Gastroenterology research and practice · 2019Review
- Regulation of RhoA GTPase and various transcription factors in the RhoA pathway.Journal of cellular physiology · 2018Review
- MicroRNA-105 is involved in TNF-α-related tumor microenvironment enhanced colorectal cancer progression.Cell death & disease · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor (TGF)-β1 plays several roles in a variety of cellular functions. TGF-β1 transmits its signal through Smad transcription factor-dependent and -independent pathways. It was reported that TGF-β1 activates NF-κB and RhoA, and RhoA activates NF-κB in several kinds of cells in a Smad-independent pathway. However, the activation molecular mechanism of NF-κB by RhoA upon TGF-β1 has not been clearly elucidated. We observed that RhoA-GTP level was increased by TGF-β1 in RAW264.7 cells. RhoA-GDP and RhoGDI were bound to N- and C-terminal domains of IKKγ, respectively. Purified IKKγ facilitated GTP binding to RhoA complexed with RhoGDI. Furthermore, Dbs, a guanine nucletotide exchange factor of RhoA much more enhanced GTP binding to RhoA complexed with RhoGDI in the presence of IKKγ. Indeed, si-IKKγ abolished RhoA activation in response to TGF-β1 in cells. However, TGF-β1 stimulated the release of RhoA-GTP from IKKγ and Rho-associated kinase (ROCK), an active RhoA effector protein, directly phosphorylated IKKβ in vitro, whereas TGF-β1-activated kinase 1 activated RhoA upon TGF-β1 stimulation. Taken together, our data indicate that IKKγ facilitates RhoA activation via a guanine nucletotide exchange factor, which in turn activates ROCK to phosphorylate IKKβ, leading to NF-κB activation that induced the chemokine expression and cell migration upon TGF-β1.
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