RRC ID |
43937
|
著者 |
Itoh S, Saito T, Hirata M, Ushita M, Ikeda T, Woodgett JR, Algül H, Schmid RM, Chung UI, Kawaguchi H.
|
タイトル |
GSK-3α and GSK-3β proteins are involved in early stages of chondrocyte differentiation with functional redundancy through RelA protein phosphorylation.
|
ジャーナル |
J Biol Chem
|
Abstract |
Here we examine the roles of two isoforms of glycogen synthase kinase-3 (GSK-3), GSK-3α and GSK-3β, in skeletal development. Both isoforms were unphosphorylated and active in chondrocyte differentiation stages during SOX9 and type II collagen (COL2A1) expression. Although knock-out of both alleles of Gsk3a (Gsk3a(-/-)) or a single allele of Gsk3b (Gsk3b(+/-)) in mice did not significantly affect skeletal development, compound knock-out (Gsk3a(-/-);Gsk3b(+/-)) caused dwarfism with impairment of chondrocyte differentiation. GSK-3α and GSK-3β induced differentiation of cultured chondrocytes with functional redundancy in a cell-autonomous fashion, independently of the Wnt/β-catenin signal. Computational predictions followed by SOX9 and COL2A1 transcriptional assays identified RelA (NF-κB p65) as a key phosphorylation target of GSK-3. Among several phosphorylation residues in RelA, Thr-254 was identified as the critical phosphorylation site for GSK-3 that modulated chondrocyte differentiation. In conclusion, redundant functions of GSK-3α and GSK-3β through phosphorylation of RelA at Thr-254 play a crucial role in early stages of chondrocyte differentiation.
|
巻・号 |
287(35)
|
ページ |
29227-36
|
公開日 |
2012-8-24
|
DOI |
10.1074/jbc.M112.372086
|
PII |
S0021-9258(20)63189-1
|
PMID |
22761446
|
PMC |
PMC3436165
|
MeSH |
Animals
Bone Development / genetics
Cell Differentiation*
Cell Line
Chondrocytes / enzymology*
Chondrocytes / pathology
Collagen Type II / biosynthesis
Dwarfism / enzymology
Dwarfism / genetics
Glycogen Synthase Kinase 3 / genetics
Glycogen Synthase Kinase 3 / metabolism*
Glycogen Synthase Kinase 3 beta
Mice
Mice, Knockout
Phosphorylation / genetics
SOX9 Transcription Factor / genetics
SOX9 Transcription Factor / metabolism
Transcription Factor RelA / genetics
Transcription Factor RelA / metabolism*
Wnt Proteins / genetics
Wnt Proteins / metabolism
Wnt Signaling Pathway / genetics
beta Catenin / genetics
beta Catenin / metabolism
|
IF |
4.238
|
引用数 |
27
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
ATDC5(RCB0565) |