Type III TGF-beta receptor-independent signalling of TGF-beta2 via TbetaRII-B, an alternatively spliced TGF-beta type II receptor
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Transforming growth factor-beta (TGF-beta) signals through membrane-bound serine/threonine kinase receptors, which upon stimulation phosphorylate Smad proteins and thereby trigger their nuclear translocation and transcriptional activity. Although the three mammalian isoforms of TGF-beta are highly homologous at the level of sequence, analysis of their in vivo function by gene knockouts revealed striking differences, suggesting no significant functional redundancy between TGF-beta1, -2 and -3. While signal transduction by TGF-beta1 has been well characterized, receptor binding and activation by the TGF-beta2 isoform is less well understood. Here, we show that TbetaRII-B, an alternatively spliced variant of the TGF-beta type II receptor, is a TGF-beta2 binding receptor, which mediates signalling via the Smad pathway in the absence of any TGF-beta type III receptor (TbetaRIII). L6 cells lacking endogenous TbetaRIII as well as TbetaRII-B do not respond to TGF-beta2. Transfection of these cells with TbetaRII-B restores TGF-beta2 sensitivity. The expression of TbetaRII-B is restricted to cells originating from tissues such as bone where the isoform TGF-beta2 has a predominant role. This reflects the importance of this receptor in TGF-beta isoform-specific signalling.
Details
Original language | English |
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Pages (from-to) | 480-90 |
Number of pages | 11 |
Journal | The EMBO journal |
Volume | 20 |
Issue number | 3 |
Publication status | Published - 1 Feb 2001 |
Peer-reviewed | Yes |
External IDs
PubMedCentral | PMC133482 |
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Scopus | 0035254335 |
ORCID | /0000-0002-0320-4223/work/150884983 |
Keywords
Keywords
- Activin Receptors, Type I, Alternative Splicing, Amino Acid Sequence, Animals, Cell Line, DNA, Complementary/genetics, DNA-Binding Proteins/metabolism, Disulfides/chemistry, Gene Expression, Glycosylation, Humans, In Vitro Techniques, Macromolecular Substances, Molecular Sequence Data, Protein Serine-Threonine Kinases/chemistry, Proteoglycans/chemistry, RNA, Messenger/genetics, Receptor, Transforming Growth Factor-beta Type I, Receptor, Transforming Growth Factor-beta Type II, Receptors, Transforming Growth Factor beta/chemistry, Sequence Homology, Amino Acid, Signal Transduction, Smad2 Protein, Trans-Activators/metabolism, Transfection, Transforming Growth Factor beta/metabolism, Transforming Growth Factor beta2