Calmodulin-dependent kinase II regulates Dlx5 during osteoblast differentiation.
Calmodulin-dependent kinase II (CaMKII) acts as a key regulator of osteoblast differentiation. CaMKII is a Ca(2+)-activated serine/threonine kinase and it regulates the activity of target proteins by phosphorylation. Dlx5 transcription factor plays crucial roles in osteoblast differentiation. The expression of Dlx5 is regulated by several osteogenic signaling pathways from early stages of osteoblastogenesis. In addition, Dlx5 can be phosphorylated and activated by p38, suggesting that the function of Dlx5 can be also modulated by post-translational modification. Although CaMKII and Dlx5 both play crucial roles during osteoblast differentiation, the interaction between CaMKII and Dlx5 has not been investigated. In the current study, we examined the effects CamKII on the function of Dlx5. We found that CaMKII phosphorylates Dlx5, and that CaMKII increases the protein stability and the osteoblastogenic transactivation activity of Dlx5. Conversely, a CaMKII inhibitor KN-93 decreased the osteogenic and transactivation activities of Dlx5. These results indicate that CaMKII regulates osteoblast differentiation, at least in part, by increasing the protein stability and the transcriptional activity of Dlx5.
Seo
Jae Hee
JH
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea.
Jin
Yun-Hye
YH
Jeong
Hyung Min
HM
Kim
Yeon-Jin
YJ
Jeong
Hye Gwang
HG
Yeo
Chang-Yeol
CY
Lee
Kwang-Youl
KY
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015533:Transcriptional Activation
D055396:Bone Morphogenetic Protein 2; D018398:Homeodomain Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2