| First Author | Itoh S | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 35 | Pages | 29227-36 |
| PubMed ID | 22761446 | Mgi Jnum | J:190241 |
| Mgi Id | MGI:5448482 | Doi | 10.1074/jbc.M112.372086 |
| Citation | Itoh S, et al. (2012) GSK-3alpha and GSK-3beta proteins are involved in early stages of chondrocyte differentiation with functional redundancy through RelA protein phosphorylation. J Biol Chem 287(35):29227-36 |
| abstractText | Here we examine the roles of two isoforms of glycogen synthase kinase-3 (GSK-3), GSK-3alpha and GSK-3beta, 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-3alpha and GSK-3beta induced differentiation of cultured chondrocytes with functional redundancy in a cell-autonomous fashion, independently of the Wnt/beta-catenin signal. Computational predictions followed by SOX9 and COL2A1 transcriptional assays identified RelA (NF-kappaB 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-3alpha and GSK-3beta through phosphorylation of RelA at Thr-254 play a crucial role in early stages of chondrocyte differentiation. |
