Premium
TAK1 mediates BMP signaling in cartilage
Author(s) -
Greenblatt Matthew B.,
Shim JaeHyuck,
Glimcher Laurie H.
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.05222.x
Subject(s) - smad , microbiology and biotechnology , mapk/erk pathway , bone morphogenetic protein , signal transduction , crosstalk , phosphorylation , cartilage , phenotype , kinase , chemistry , p38 mitogen activated protein kinases , protein kinase a , biology , anatomy , genetics , physics , optics , gene
Although many signals are capable of activating MAPK signaling cascades in chondrocytes in vitro , the function of these pathways remains unclear in vivo . Here we report the phenotype of mice with a conditional deletion of TGF‐β‐activated kinase 1 (TAK1), a MAP3K family member, in cartilage using the collagen 2α promoter. These mice display chondrodysplasia characterized by neonatal‐onset runting, delayed formation of secondary ossification centers, and defects in formation of the elbow and tarsal joints. This constellation of defects resembles the phenotype of mice deficient for receptors or ligands involved in signaling by BMP family members. Chondrocytes from these mice show evidence of defective BMP signaling in vivo and in vitro . Surprisingly, deletion of TAK1 seems to affect not only activation of the p38 MAPK signaling cascade, but also activation of the BMP‐responsive Smad1/5/8. Biochemical analysis suggests that TAK1 can interact with Smad proteins and promote their activation through phosphorylation, revealing a previously unrecognized crosstalk between the MAPK and Smad arms of BMP signaling.