title: Protein kinase A phosphorylates and regulates the osteogenic activity of Dlx5.
abstract: Dlx5 transcription factor plays important roles in osteoblast differentiation and its transcription is regulated by many osteogenic signals including BMP-2. Recent studies suggest that the function of Dlx5 is also regulated post-translationally by protein kinases such as p38 and CaMKII. Protein kinase A (PKA) is involved in several steps of osteoblast differentiation and its activity has been shown necessary, yet not sufficient, for BMP-induced osteoblast differentiation. PKA is a ubiquitous cellular kinase that phosphorylates serine and threonine residues(s) of target proteins. In this study, we investigated the potential regulation of Dlx5 function by PKA in osteoblast differentiation. We found that PKA phosphorylates Dlx5 and that PKA activation increases the protein stability, osteogenic activity and transcriptional activity of Dlx5. We also found that BMP-2 increases the protein level of Dlx5 in a PKA activity-dependent manner. These results suggest that PKA activity enhances the osteogenic function of Dlx5, at least in part, through protein stabilization and that BMP-2 regulates the osteogenic function of Dlx5, at least in part, through PKA.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Younho
authors.initials: Y
authors.lastname: Han
authors.forename: Yun-Hye
authors.initials: YH
authors.lastname: Jin
authors.forename: Jinah
authors.initials: J
authors.lastname: Yum
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Jeong
authors.forename: Joong-Kook
authors.initials: JK
authors.lastname: Choi
authors.forename: Chang-Yeol
authors.initials: CY
authors.lastname: Yeo
authors.forename: Kwang-Youl
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D014158:Transcription, Genetic
chemical_list: D055396:Bone Morphogenetic Protein 2; C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; D017868:Cyclic AMP-Dependent Protein Kinases