Integration of phosphatidylinositol 3-kinase, Akt kinase, and Smad signaling pathway in BMP-2-induced osterix expression.
basic_science · Level V
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- Record sourced from PubMed, PMID 20872216.
- Also identified by DOI 10.1007/s00223-010-9419-3 and PMC identifier 3055166.
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Abstract
Osterix (Osx), a BMP-2-regulated transcription factor, controls expression of genes essential for osteoblast differentiation. Using progressive deletion of the Osx promoter, we characterized a Smad binding element (SBE) between -552 and -839 bp from its transcription start site. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed binding and in vivo recruitment of Smads 1 and 5 to the Osx SBE. Inactivation of PI 3-kinase by the pharmacologic inhibitor Ly294002 or by dominant negative (DN) enzyme significantly blocked BMP-2-induced Osx protein and mRNA expression and Osx transcription. Finally, both DN PI 3-kinase and DN Akt significantly attenuated Smad 5-dependent transcription of Osx, demonstrating the first evidence for a concerted action of PI 3-kinase/Akt signaling with BMP-specific Smads for expression of Osx.
Medical subject headings
- Bone Morphogenetic Protein 2
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
- Signal Transduction
- Smad Proteins
- Transcription Factors