ArticleThe Journal of biological chemistry2012
The TGFβ receptor-interacting protein km23-1/DYNLRB1 plays an adaptor role in TGFβ1 autoinduction via its association with Ras.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Serum biomarkers associated with baseline clinical severity in young steroid-naïve Duchenne muscular dystrophy boys.Human molecular genetics · 2020Trial
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- AMPK inhibits Smad3-mediated autoinduction of TGF-β1 in gastric cancer cells.Journal of cellular and molecular medicine · 2021Article
- DYNLRB1 is essential for dynein mediated transport and neuronal survival.Neurobiology of disease · 2020Article
- TGF-β Signaling.Biomolecules · 2020Review
- km23-1/DYNLRB1 regulation of MEK/ERK signaling and R-Ras in invasive human colorectal cancer cells.Cell biology international · 2020Article
- Signaling Receptors for TGF-β Family Members.Cold Spring Harbor perspectives in biology · 2016Review
- Requirement for protein kinase A in the phosphorylation of the TGFβ receptor-interacting protein km23-1 as a component of TGFβ downstream effects.Experimental cell research · 2013Article
- A dynein motor attachment complex regulates TGFß/Smad3 signaling.International journal of biological sciences · 2013Article
- Decreased tumor progression and invasion by a novel anti-cell motility target for human colorectal carcinoma cells.PloS one · 2013Article
- Role of km23-1 in RhoA/actin-based cell migration.Biochemical and biophysical research communications · 2012Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
We have previously elucidated the signaling events that are required for TGFβ1 autoinduction (Yue, J., and Mulder, K. M. (2000) J. Biol. Chem. 275, 30765-30773). Further, we have reported that the TGFβ receptor (TβR)-interacting protein km23-1 plays an important role in TGFβ signal transduction (Jin, Q., Ding, W., and Mulder, K. M. (2007) J. Biol. Chem. 282, 19122-19132). Here we examined the role of km23-1 in TGFβ1 autoinduction in TGFβ-sensitive epithelial cells. siRNA blockade of km23-1 reduced TGFβ1 mRNA expression, as well as DNA binding and transcriptional activation of the relevant activator protein-1 site in the human TGFβ1 promoter. Further, knockdown of km23-1 inhibited TGFβ-mediated activation of ERK and JNK, phosphorylation of c-Jun, and transactivation of the c-Jun promoter. Sucrose gradient analyses indicate that km23-1 was present in lipid rafts together with Ras and TβRII after TGFβ treatment. Immunoprecipitation/blot analyses revealed the formation of a TGFβ-inducible complex between Ras and km23-1 in vivo within minutes of TGFβ addition. Moreover, we demonstrate for the first time that km23-1 is required for Ras activation by TGFβ. Our results indicate that km23-1 is required for TGFβ1 autoinduction through Smad2-independent Ras/ERK/JNK pathways. More importantly, our findings demonstrate that km23-1 functions as a critical adaptor coupling TβR activation to activation of Ras effector pathways downstream.
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Registered trials
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