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PMID: 11438668 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Axin facilitates Smad3 activation in the transforming growth factor beta signaling pathway.

Molecular and cellular biology ·Vol. 21 ·No. 15 ·2001-08-00 ·Pages 5132-41

Furuhashi M, Yagi K, Yamamoto H, Furukawa Y, Shimada S, Nakamura Y, Kikuchi A, Miyazono K, Kato M

Abstract

Axin acts as a negative regulator in Wnt signaling through interaction with various molecules involved in this pathway, including beta-catenin, adenomatous polyposis coli, and glycogen synthase kinase 3beta. We show here that Axin also regulates the effects of Smad3 on the transforming growth factor beta (TGF-beta) signaling pathway. In the absence of activated TGF-beta receptors. Axin physically interacted with Smad3 through its C-terminal region located between the beta-catenin binding site and Dishevelled-homologous domain. An Axin homologue, Axil (also called conductin), also interacted with Smad3. In the absence of ligand stimulation, Axin was colocalized with Smad3 in the cytoplasm in vivo. Upon receptor activation, Smad3 was strongly phosphorylated by TGF-beta type I receptor (TbetaR-I) in the presence of Axin, and dissociated from TbetaR-I and Axin. Moreover, the transcriptional activity of TGF-beta was enhanced by Axin and repressed by an Axin mutant which is able to bind to Smad3. Axin may thus function as an adapter of Smad3, facilitating its activation by TGF-beta receptors for efficient TGF-beta signaling.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Axin Protein Binding Sites Blotting, Northern COS Cells Cell Line Cells, Cultured Cytoplasm/metabolism Cytoskeletal Proteins/metabolism DNA, Complementary/metabolism DNA-Binding Proteins/metabolism Dishevelled Proteins Humans Immunoblotting Ligands Luciferases/metabolism Microscopy, Confocal Microscopy, Fluorescence Models, Genetic Phosphoproteins/metabolism Phosphorylation Precipitin Tests Protein Binding Protein Structure, Tertiary Proteins/genetics,metabolism,physiology Proto-Oncogene Proteins/metabolism RNA, Messenger/metabolism Repressor Proteins Signal Transduction Smad3 Protein Trans-Activators/metabolism Transcription, Genetic Transcriptional Activation Transfection Transforming Growth Factor beta/metabolism Wnt Proteins Zebrafish Proteins beta Catenin
Chemicals
Adaptor Proteins, Signal Transducing Axin Protein CTNNB1 protein, human Cytoskeletal Proteins DNA, Complementary DNA-Binding Proteins Dishevelled Proteins Ligands Phosphoproteins Proteins Proto-Oncogene Proteins RNA, Messenger Repressor Proteins SMAD3 protein, human Smad3 Protein Trans-Activators Transforming Growth Factor beta Wnt Proteins Zebrafish Proteins beta Catenin Luciferases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Furuhashi M
Department of Biochemistry, The Japanese Foundation for Cancer Research (JFCR) Cancer Institute, Toshima-ku, Tokyo 170-8455, Japan.
Yagi K
Yamamoto H
Furukawa Y
Shimada S
Nakamura Y
Kikuchi A
Miyazono K
Kato M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.15.5132-5141.2001
Published
2001-08-00
Pages
5132-41
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC87238
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.21.15.5132-5141.2001 PMC Full Text View journal details
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