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)