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PMID: 17251195 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The Delta intracellular domain mediates TGF-beta/Activin signaling through binding to Smads and has an important bi-directional function in the Notch-Delta signaling pathway.

Nucleic acids research ·Vol. 35 ·No. 3 ·2007-00-00 ·Pages 912-22

Hiratochi M, Nagase H, Kuramochi Y, Koh CS, Ohkawara T, Nakayama K

Abstract

Delta is a major transmembrane ligand for Notch receptor that mediates numerous cell fate decisions. The Notch signaling pathway has long been thought to be mono-directional, because ligands for Notch were generally believed to be unable to transmit signals into the cells expressing them. However, we showed here that Notch also supplies signals to neighboring mouse neural stem cells (NSCs). To investigate the Notch-Delta signaling pathway in a bi-directional manner, we analyzed functional roles of the intracellular domain of mouse Delta like protein 1 (Dll1IC). In developing mouse NSCs, Dll1IC, which is released from cell membrane by proteolysis, is present in the nucleus. Furthermore, we screened for transcription factors that bind to Dll1IC and demonstrated that Dll1IC binds specifically to transcription factors involved in TGF-beta/Activin signaling--Smad2, Smad3 and Smad4--and enhances Smad-dependent transcription. In addition, the results of the present study indicated that over-expression of Dll1IC in embryonic carcinoma P19 cells induced neurons, and this induction was blocked by SB431542, which is a specific inhibitor of TGF-beta/Activin signaling. These observations strongly suggested that Dll1IC mediates TGF-beta/Activin signaling through binding to Smads and plays an important role for bi-directional Notch-Delta signaling pathway.

MeSH Terms
Activins/physiology Amino Acid Sequence Animals Binding Sites Calcium-Binding Proteins Cell Differentiation Cell Line, Tumor Cell Nucleus/chemistry Cells, Cultured Evolution, Molecular Intercellular Signaling Peptides and Proteins/analysis,chemistry,metabolism Mice Molecular Sequence Data Neurons/cytology,metabolism Protein Structure, Tertiary Receptor, Notch1/metabolism Sequence Homology, Amino Acid Signal Transduction Smad Proteins/metabolism Stem Cells/cytology,metabolism Transcription, Genetic Transforming Growth Factor beta/physiology
Chemicals
Calcium-Binding Proteins Dlk1 protein, mouse Intercellular Signaling Peptides and Proteins Notch1 protein, mouse Receptor, Notch1 Smad Proteins Transforming Growth Factor beta Activins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hiratochi Masahiro
Department of Anatomy, Shinshu University, School of Medicine, Matsumoto, Nagano 390-8621, Japan.
Nagase Hisashi
Kuramochi Yu
Koh Chang-Sung
Ohkawara Takeshi
Nakayama Kohzo
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkl1128
Published
2007-00-00
Epub
2007-00-23
Pages
912-22
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1807952
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkl1128 PMC Full Text View journal details
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