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Phosphorylation of ...
Phosphorylation of Smad7 at Ser-249 does not interfere with its inhibitory role in transforming growth factor-beta-dependent signaling but affects Smad7-dependent transcriptional activation
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- Pulaski, Lukasz (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Landström, Maréne (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Heldin, Carl-Henrik (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Souchelnytskyi, Serhiy (author)
- Karolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning
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(creator_code:org_t)
- 2001
- 2001
- English.
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 276:17, s. 14344-14349
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Smad proteins are major components in the intracellular signaling pathway of transforming growth factor-beta (TGF-beta), and phosphorylation is an important mechanism in regulation of their functions. Smad7 was identified as a potent inhibitor of TGF-beta-dependent signaling. We have identified serine 249 in Smad7 as a major phosphorylation site, the phosphorylation of which was not affected by TGF-beta1. Abrogation of the phosphorylation by substitution of Ser-249 with alanine or aspartic acid residues did not affect the ability of Smad7 to inhibit TGF-beta1 and BMP7 signaling. No differences were found in the stability or in the intracellular distribution of Smad7 mutants compared with the wild-type molecule. However, Smad7 fused to the DNA-binding domain of GAL4 induced transcription from a reporter with mutated TATA minimal promoter in a Ser-249-dependent manner. Moreover, a reporter with the SV40 minimal promoter was inhibited by GAL4-Smad7, and this effect was also dependent on Ser-249 phosphorylation. The amplitude of effects on transcriptional regulation was dependent on cell type. Our results suggest that phosphorylation of Smad7, unlike phosphorylation of the receptor-regulated Smads, does not regulate TGF-beta signaling but rather affects TGF-beta-independent effects of Smad7 on transcriptional regulation.
Keyword
- 3T3 Cells
- Amino Acid Sequence
- Animals
- Aspartic Acid/chemistry
- Bone Morphogenetic Proteins/metabolism
- COS Cells
- Cell Nucleus/metabolism
- DNA/metabolism
- DNA-Binding Proteins/genetics/*metabolism/*physiology
- Genes; Reporter
- Ligands
- Luciferases/metabolism
- Mice
- Microscopy; Fluorescence
- Molecular Sequence Data
- Mutation
- Phosphorylation
- Promoter Regions (Genetics)
- Protein Structure; Tertiary
- Research Support; Non-U.S. Gov't
- Serine/chemistry
- Signal Transduction
- Time Factors
- Trans-Activation (Genetics)
- Trans-Activators/genetics/*metabolism/*physiology
- Transcription; Genetic
- Transfection
- Transforming Growth Factor beta/*metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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