title: Casein kinase 2 beta-subunit is a regulator of bone morphogenetic protein 2 signaling.
abstract: Bone morphogenetic proteins (BMPs) play a crucial role during embryonic development and regulate processes as diverse as neurogenesis, skeletal formation, and hematopoesis. They signal through a hetero-oligomer complex of BMP receptors. Binding of the ligand to the receptors activates several pathways, including Smad and p38. BMP signaling is controlled in the extracellular space, the plasma membrane, and the intracellular space; however, the mechanism of receptor signaling at the plasma membrane and proteins that regulate this process still need to be identified. The experiments presented here identify the protein kinase casein kinase II (CK2) as a BMP receptor type Ia (BRIa) interacting protein. Fluorescence resonance energy transfer revealed that this interaction occurs at the plasma membrane. BMP2 stimulation of C2C12 cells leads to the release of CK2 from BRIa. Blocking this interaction with specific peptides that inhibit the binding sites for CK2 on BRIa demonstrated a redistribution of BRIa on the plasma membrane. Signaling was initiated once CK2 was released from BRIa, leading to the mineralization of C2C12 cells. These data suggest that CK2 is a negative regulator of BMP signaling and osteoblast differentiation.
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Bragdon
authors.forename: Shayamala
authors.initials: S
authors.lastname: Thinakaran
authors.forename: Oleksandra
authors.initials: O
authors.lastname: Moseychuk
authors.forename: Daniel
authors.initials: D
authors.lastname: King
authors.forename: Kira
authors.initials: K
authors.lastname: Young
authors.forename: David W
authors.initials: DW
authors.lastname: Litchfield
authors.forename: Nils O
authors.initials: NO
authors.lastname: Petersen
authors.forename: Anja
authors.initials: A
authors.lastname: Nohe
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D047390:Casein Kinase II / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005799:Genes, Dominant / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D010455:Peptides / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D010455:Peptides; D051785:Smad Proteins; D047390:Casein Kinase II; D052005:Bone Morphogenetic Protein Receptors, Type I