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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activin Receptors, Type I*
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Alternative Splicing
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Amino Acid Sequence
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Animals
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Cell Line
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DNA, Complementary / genetics
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DNA, Complementary / isolation & purification
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DNA-Binding Proteins / metabolism
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Disulfides / chemistry
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Gene Expression
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Glycosylation
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Humans
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In Vitro Techniques
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Macromolecular Substances
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Molecular Sequence Data
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / metabolism
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Proteoglycans / chemistry
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Proteoglycans / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptor, Transforming Growth Factor-beta Type I
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / chemistry
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Receptors, Transforming Growth Factor beta / genetics*
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Receptors, Transforming Growth Factor beta / metabolism*
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Sequence Homology, Amino Acid
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Signal Transduction
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Smad2 Protein
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Trans-Activators / metabolism
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Transfection
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Transforming Growth Factor beta / metabolism*
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Transforming Growth Factor beta2
Substances
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DNA, Complementary
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DNA-Binding Proteins
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Disulfides
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Macromolecular Substances
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Proteoglycans
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RNA, Messenger
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Receptors, Transforming Growth Factor beta
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SMAD2 protein, human
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Smad2 Protein
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TGFB2 protein, human
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Trans-Activators
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Transforming Growth Factor beta
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Transforming Growth Factor beta2
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betaglycan
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Protein Serine-Threonine Kinases
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I
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Receptor, Transforming Growth Factor-beta Type II