TAK1 is an Essential Regulator of BMP Signalling in Cartilage

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TAK1 is an Essential Regulator of BMP Signalling in Cartilage

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dc.contributor.author Shim, Jae-Hyuck
dc.contributor.author Xie, Min
dc.contributor.author Schneider, Michael D
dc.contributor.author Greenblatt, Matthew Blake
dc.contributor.author Glimcher, Laurie Hollis
dc.contributor.author Gygi, Steven P.
dc.contributor.author Zou, Weigou
dc.contributor.author Zhai, Bo
dc.date.accessioned 2011-05-19T02:15:10Z
dc.date.issued 2009
dc.identifier.citation Shim, Jae-Hyuck, Matthew B. Greenblatt, Min Xie, Michael D. Schneider, Weiguo Zou, Bo Zhai, Steven Gygi, and Laurie H. Glimcher. 2009. TAK1 is an essential regulator of BMP signalling in cartilage. The EMBO Journal 28(14): 2028-2041. en_US
dc.identifier.issn 0261-4189 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4891679
dc.description.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. Tak1\(^{col2}\) 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. en_US
dc.language.iso en_US en_US
dc.publisher Nature Publishing Group en_US
dc.relation.isversionof doi:10.1038/emboj.2009.162 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699391/pdf/ en_US
dash.license LAA
dc.subject BMP en_US
dc.subject cartilage en_US
dc.subject Smad en_US
dc.subject TAK1 en_US
dc.subject TGFβ en_US
dc.title TAK1 is an Essential Regulator of BMP Signalling in Cartilage en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal The EMBO Journal en_US
dash.depositing.author Glimcher, Laurie Hollis
dc.date.available 2011-05-19T02:15:10Z
dash.affiliation.other SPH^Immunology and Infectious Diseases Immunology en_US
dash.affiliation.other HMS^Stipendees - Enrichment Programs Stip en_US
dash.affiliation.other HMS^Stipendees - MD-PhD en_US
dash.affiliation.other HMS^Stipendees - Div of Medical Sciences en_US
dash.affiliation.other HMS^Cell Biology en_US
dash.affiliation.other SPH^Immunology and Infectious Diseases Immunology en_US
dash.affiliation.other SPH^Immunology and Infectious Diseases TPH en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US

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