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Interactome of tran...
Interactome of transforming growth factor-beta type I receptor (T beta RI) : Inhibition of TGF beta signaling by Epac1
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- Conrotto, Paolo (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Yakymovych, Ihor (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Yakymovych, Mariya (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Souchelnytskyi, Serhiy (författare)
- Karolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning
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(creator_code:org_t)
- 2006-12-15
- 2007
- Engelska.
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:1, s. 287-297
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Transforming growth factor-beta (TGF beta) is a potent regulator of cell growth, differentiation, and apoptosis. Type I TGF beta receptor (T beta RI) is the key receptor for initiation of intracellular signaling by TGF beta. Here we report proteomics-based identification of proteins that form a complex with T beta RI. Using 2D-GE and MALDI TOF mass spectrometry, we identified 16 proteins that specifically interacted with a GST-fused T beta RI Thr204Asp construct with constitutively active serine/threonine kinase. We confirmed interactions of the receptor with cAMP regulated guanine nucleotide exchange factor 1 (Epac1), alpha-spectrin, PIASy, and alpha-catenin proteins using immunoblotting. Interaction of the receptor with Epac1 required intact kinase activity of T beta RI but was not affected by deletion of cAMP-binding domain of Epac1. TGF beta 1-induced C-terminal phosphorylation of Smad2 was inhibited in vivo and in vitro in the presence of Epac1. Epac1 inhibited also TGF beta 1/T beta RI-dependent transcriptional activation, as evaluated by luciferase reporter assays. We observed that expression of Epac1 counteracted TGF beta/T beta RI-dependent decrease of cell adhesion and TGF beta/T beta RI-induced stimulation of cell migration. Thus, we have reported novel T beta RI-interacting proteins and have shown that Epac1 inhibited TGF beta-dependent regulation of cell migration and adhesion.
Nyckelord
- proteomics
- TGF beta
- T beta RI
- Epac1
- transcription
- migration
- adhesion
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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