TAK1 is an essential regulator of BMP signalling in cartilage
File(s)
Author(s)
Type
Journal Article
Abstract
TGFβ activated kinase 1 (TAK1), a member of the MAPKKK family, controls diverse functions ranging from innate and adaptive immune system activation to vascular development and apoptosis. To analyse the in vivo function of TAK1 in cartilage, we generated mice with a conditional deletion of Tak1 driven by the collagen 2 promoter. Tak1col2 mice displayed severe chondrodysplasia with runting, impaired formation of secondary centres of ossification, and joint abnormalities including elbow dislocation and tarsal fusion. This phenotype resembled that of bone morphogenetic protein receptor (BMPR)1 and Gdf5‐deficient mice. BMPR signalling was markedly impaired in TAK1‐deficient chondrocytes as evidenced by reduced expression of known BMP target genes as well as reduced phosphorylation of Smad1/5/8 and p38/Jnk/Erk MAP kinases. TAK1 mediates Smad1 phosphorylation at C‐terminal serine residues. These findings provide the first in vivo evidence in a mammalian system that TAK1 is required for BMP signalling and functions as an upstream activating kinase for Smad1/5/8 in addition to its known role in regulating MAP kinase pathways. Our experiments reveal an essential role for TAK1 in the morphogenesis, growth, and maintenance of cartilage.
Date Issued
2009-07-22
Date Acceptance
2009-05-18
Citation
The EMBO Journal, 2009, 28 (14), pp.2028-2041
ISSN
0261-4189
Publisher
EMBO Press
Start Page
2028
End Page
2041
Journal / Book Title
The EMBO Journal
Volume
28
Issue
14
Copyright Statement
© 2009 European Molecular Biology Organization. The EMBO Journal is published by Nature
Publishing Group on behalf of European
Molecular Biology Organization. This article is licensed
under a Creative Commons Attribution-NoncommercialShare Alike 3.0 Licence. [http://creativecommons.org/licenses/by-nc-sa/3.0/]
Publishing Group on behalf of European
Molecular Biology Organization. This article is licensed
under a Creative Commons Attribution-NoncommercialShare Alike 3.0 Licence. [http://creativecommons.org/licenses/by-nc-sa/3.0/]
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000268648900006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
BMP
cartilage
Smad
TAK1
TGF beta
FAMILY MEDIATOR SMAD1
TGF-BETA RECEPTOR
GROWTH-PLATE
KINASE TAK1
IN-VIVO
CHONDROCYTE DIFFERENTIATION
INDIAN-HEDGEHOG
II RECEPTOR
PATHWAYS
MICE
Publication Status
Published
Date Publish Online
2009-06-18