title: Protein kinase a phosphorylates Dlx3 and regulates the function of Dlx3 during osteoblast differentiation.
abstract: Protein kinase A (PKA), a serine/threonine kinase, regulates bone formation, and enhances Bone morphogenetic protein (BMP)-induced osteoblast differentiation. However, the mechanisms of how PKA controls the cellular response to BMP are not well known. We investigated the effects of modulating PKA activity during BMP2-induced osteoblast differentiation, and found that PKA regulates the function of Dlx3. Dlx3 plays crucial roles in osteoblast differentiation and it is expressed in most skeletal elements during development. We found that PKA activation increases BMP2-induced expression of Dlx3 protein, and enhances the protein stability, DNA binding, and transcriptional activity of Dlx3. In addition, PKA activation induces the phosphorylation of Dlx3 at consensus PKA phosphorylation target site(s). Lastly, substitution of serine 10 in Dlx3 to alanine significantly reduces, if not completely abolishes, the phosphorylation of Dlx3 and the regulation of Dlx3 function by PKA. These results suggest that Dlx3 is a novel target of PKA, and that PKA mediates BMP signaling during osteoblast differentiation, at least in part, by phosphorylating Dlx3 and modulating the protein stability and function of Dlx3.
authors.affiliation: College of Pharmacy and Research Institute of Drug development, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Hyung Min
authors.initials: HM
authors.lastname: Jeong
authors.forename: You Hee
authors.initials: YH
authors.lastname: Choi
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Joong-Kook
authors.initials: JK
authors.lastname: Choi
authors.forename: Chang-Yeol
authors.initials: CY
authors.lastname: Yeo
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
authors.forename: ChangJu
authors.initials: C
authors.lastname: Chun
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D010766:Phosphorylation; D055550:Protein Stability; D012694:Serine / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D055396:Bone Morphogenetic Protein 2; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D007546:Isoquinolines; D013449:Sulfonamides; D014157:Transcription Factors; D005576:Colforsin; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: Dlx3; OSTEOBLAST DIFFERENTIATION; PROTEIN KINASE A; PROTEIN STABILITY; TRANSCRIPTIONAL ACTIVITY