Premium
Type III TGF‐β receptor‐independent signalling of TGF‐β2 via TβRII‐B, an alternatively spliced TGF‐β type II receptor
Author(s) -
Rotzer Diana,
Roth Martin,
Lutz Marion,
Lindemann Dirk,
Sebald Walter,
Knaus Petra
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.3.480
Subject(s) - tgf beta receptor 2 , biology , receptor , smad , acvrl1 , transforming growth factor beta , endoglin , signal transduction , gene isoform , tgf beta signaling pathway , microbiology and biotechnology , r smad , smad2 protein , interleukin 21 receptor , transforming growth factor , biochemistry , tgf alpha , growth factor , gene , stem cell , cd34
Transforming growth factor‐β (TGF‐β) 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‐β 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‐β1, ‐2 and ‐3. While signal transduction by TGF‐β1 has been well characterized, receptor binding and activation by the TGF‐β2 isoform is less well understood. Here, we show that TβRII‐B, an alternatively spliced variant of the TGF‐β type II receptor, is a TGF‐β2 binding receptor, which mediates signalling via the Smad pathway in the absence of any TGF‐β type III receptor (TβRIII). L6 cells lacking endogenous TβRIII as well as TβRII‐B do not respond to TGF‐β2. Transfection of these cells with TβRII‐B restores TGF‐β2 sensitivity. The expression of TβRII‐B is restricted to cells originating from tissues such as bone where the isoform TGF‐β2 has a predominant role. This reflects the importance of this receptor in TGF‐β isoform‐specific signalling.