BMP enhances transcriptional responses to NGF during PC12 cell differentiation
2005 (English)In: Neurochemical Research, ISSN 0364-3190, Vol. 30, no 6-7, 753-65 p.Article in journal (Other academic) Published
Bone morphogenetic proteins (BMPs) enhance neurite outgrowth in nerve growth factor (NGF)-stimulated PC12 cells. To investigate the mechanism of this potentiating effect, real-time PCR was used to analyze the expression of 45 selected genes. A robust increase in expression of 10 immediate early genes including Egr1-4, Hes1, Junb, Jun and Fos was observed already after 1 h treatment with NGF alone. NGF plus BMP4 further increased these transcripts at 1 h and activated 18 additional genes. BMP4 alone induced Smad6, Mtap1b and Hes1. Egr3 was the gene most strongly upregulated by NGF and BMP4. However, luciferase assays showed that the cloned Egr3 proximal promoter was not involved in the BMP4 potentiation. Blocking Egr3 and Junb function by dominant-negative constructs reduced neurite outgrowth under stimulating conditions, proving that activation of members of both the Egr and Jun families is necessary for maximal PC12 cell response to NGF and BMP4.
Place, publisher, year, edition, pages
2005. Vol. 30, no 6-7, 753-65 p.
Animals, Base Sequence, Bone Morphogenetic Proteins/*physiology, Cell Differentiation/*drug effects, Cluster Analysis, DNA Primers, Early Growth Response Protein 3/genetics, Gene Expression Regulation/genetics/physiology, Nerve Growth Factor/*pharmacology, PC12 Cells, Polymerase Chain Reaction, Promoter Regions (Genetics), Rats, Research Support; Non-U.S. Gov't, Transcription; Genetic/drug effects/*physiology
IdentifiersURN: urn:nbn:se:uu:diva-75413DOI: 10.1007/s11064-005-6868-6PubMedID: 16187211OAI: oai:DiVA.org:uu-75413DiVA: diva2:103323