TAK1 is an essential regulator of BMP signalling in cartilage

@article{Shim2009TAK1IA,
  title={TAK1 is an essential regulator of BMP signalling in cartilage},
  author={Jae-Hyuck Shim and M. Greenblatt and M. Xie and M. Schneider and Weiguo Zou and B. Zhai and S. Gygi and L. Glimcher},
  journal={The EMBO Journal},
  year={2009},
  volume={28},
  pages={2028 - 2041}
}
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… Expand
TAK1 Regulates Cartilage and Joint Development via the MAPK and BMP Signaling Pathways
  • Lea M Gunnell, J. Jonason, +4 authors R. O’Keefe
  • Biology, Medicine
  • Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 2010
TLDR
In vivo models and in vitro cell culture studies demonstrate that loss of Tak1 results in impaired activation of the downstream MAPK target p38, as well as diminishedactivation of the BMP/SMAD signaling pathway, and demonstrate that TAK1 is a critical regulator of both MAPK and BMP signaling. Expand
Ablation of Tak1 in osteoclast progenitor leads to defects in skeletal growth and bone remodeling in mice
TLDR
Findings indicate that Tak1 functions in osteoclastogenesis in a cell-aut autonomous manner and in osteoblastogenesis and chondrogenesis in non-cell-autonomous manners. Expand
A Tak1/p38 Signaling Axis Regulates Runx2 Activity and Osteoblast Functions
TLDR
The p38 pathway is a critical regulator of Runx2 activity, connecting growth factor signaling to osteoblast differentiation, and Examination of pathways downstream of TAK1 demonstrates that p38α and p38β mediate phosphorylation and activation of Run x2 by promoting the interaction between Runx 2 and cofactor CBP. Expand
Smad7 regulates terminal maturation of chondrocytes in the growth plate.
TLDR
It is found that Smad7 is required for both axial and appendicular skeletal development and may be required to mediate cell stress responses in the growth plate during development. Expand
The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice.
TLDR
It is reported that the p38 MAPK pathway is required for normal skeletogenesis in mice, and an in vivo function for p38beta is revealed and it is established that MAPK signaling is essential for bone formation in vivo. Expand
TAK1 Expression in the Cochlea: A Specific Marker for Adult Supporting Cells
TLDR
While the role of TAK1 in the inner ear is unclear, Taker1 expression may be used as a novel marker for specific sub-populations of supporting cells in the cochlea. Expand
FGFR3 induces degradation of BMP type I receptor to regulate skeletal development.
TLDR
It is found that chondrocyte-specific deletion of BMP type I receptor a (Bmpr1a) rescued the bone overgrowth phenotype observed in Fgfr3 deficient mice by reducing chondROcyte differentiation. Expand
Smad6 is essential to limit BMP signaling during cartilage development
TLDR
The results show that Smad6 is required to limit BMP signaling during endochondral bone formation, and this is the first study to show this role in mice. Expand
Noncanonical BMP signaling regulates cyclooxygenase-2 transcription.
TLDR
The results strongly suggest that cooperative effects between canonical and noncanonical BMP signaling allow the fine-tuning of BMP transcriptional responses on specific target genes. Expand
Control of the Osteoblast Lineage by Mitogen-Activated Protein Kinase Signaling
TLDR
MAPKs transduce signals from the extracellular environment to the nucleus allowing bone cells to respond to changes in hormonal/growth factor signaling and mechanical loading, thereby optimizing bone structure to meet physiological and mechanical needs of the body. Expand
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Role of TAK1 and TAB1 in BMP signaling in early Xenopus development
TLDR
Examination of the role of TAK1 and TAB1 in the dorsoventral patterning of early Xenopus embryos suggests that xTAK1 and xTAB1 function in the BMP signal transduction pathway in xenopus embryos in a cooperative manner. Expand
The TGFβ activated kinase TAK1 regulates vascular development in vivo
TLDR
It is suggested that TAK1 is probably an important downstream component of the TGFβ signal transduction pathway that regulates vertebrate vascular development, as heterozygosity for mutations in endoglin and ALK1 lead to the human syndromes known as hereditary hemorrhagic telangiectasia 1 and 2, respectively. Expand
The TGF beta activated kinase TAK1 regulates vascular development in vivo.
TLDR
It is suggested that TAK1 is probably an important downstream component of the TGFbeta signal transduction pathway that regulates vertebrate vascular development and as heterozygosity for mutations in endoglin and ALK1 lead to the human syndromes known as hereditary hemorrhagic telangiectasia 1 and 2, respectively, the results raise the possibility that mutations in human Tak1 might contribute to this disease. Expand
Smad4 is required for the normal organization of the cartilage growth plate.
TLDR
Data provided the first genetic evidence demonstrating that Smad4-mediated TGF-beta signals inhibit the chondrocyte hypertrophic differentiation, and are required for maintaining the normal organization of chONDrocytes in the growth plate. Expand
TAK1 Is a Master Regulator of Epidermal Homeostasis Involving Skin Inflammation and Apoptosis*
TLDR
It is demonstrated that TAK1 is the major regulator of skin inflammation as well as keratinocyte death in vivo and is a master regulator of TNF signaling in skin and regulates skin inflammation and keratinocytes death. Expand
Opposing BMP and EGF signalling pathways converge on the TGF-β family mediator Smad1
TLDR
It is reported that Smad1, which mediates BMP signals, is also a target of mitogenic growth-factor signalling through epidermal growth factor and hepatocyte growth factor receptor protein tyrosine kinases (RTKs), and Erk-mediated phosphorylation specifically inhibits the nuclear accumulation of Smad 1. Expand
Transforming Growth Factor-β-activated Kinase-1 (TAK1), a MAP3K, Interacts with Smad Proteins and Interferes with Osteogenesis in Murine Mesenchymal Progenitors*[boxs]
TLDR
It is suggested that TAK1 is a factor that is involved in the fine-tuning of BMP effects during osteogenic development that interferes with R-Smad transactivation in reporter assays and affects subcellular distribution of Smad proteins. Expand
Balancing BMP signaling through integrated inputs into the Smad1 linker.
TLDR
It is shown that linker phosphorylation restricts Smad1 activity by enabling Smad2 recognition by the HECT-domain ubiquitin ligase Smurf1, and the interplay between linkerosphorylation, Smirf-dependent ubiquitination, and nucleoporin exclusion enables regulation of BMP action by diverse signals and biological contexts. Expand
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TLDR
Results show that ECSit functions as an essential component in two important signal transduction pathways and establishes a novel role for Ecsit as a cofactor for Smad proteins in the Bmp signaling pathway. Expand
Id: A Target of BMP Signaling
TLDR
Growing evidence suggests that Id proteins may play crucial roles in angiogenesis, neurogenesis, and osteogenesis and act as key molecules in regulating biological responses induced by BMPs and TGF-β. Expand
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