Sprouty genes are expressed in osteoblasts and inhibit fibroblast growth factor-mediated osteoblast responses
| Autor: | Xuehui Yang, Dmitry Kovalenko, Robert J. Nadeau, Robert Friesel, Pei-Yu Chen, Olga Zubanova, J. B. Webster |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
endocrine system
Endocrinology Diabetes and Metabolism Cellular differentiation Immunoblotting Biology Protein Serine-Threonine Kinases Fibroblast growth factor Cell Line Mice Endocrinology Animals Orthopedics and Sports Medicine RNA Messenger Protein Kinase Inhibitors Adaptor Proteins Signal Transducing Feedback Physiological FGF10 Osteoblasts Fibroblast growth factor receptor 2 Reverse Transcriptase Polymerase Chain Reaction Intracellular Signaling Peptides and Proteins Membrane Proteins Proteins Cell Differentiation Fibroblast growth factor receptor 4 Fibroblast growth factor receptor 3 Cell biology Fibroblast Growth Factors Proto-Oncogene Proteins c-raf Fibroblast growth factor receptor SPRY2 Cancer research |
| Zdroj: | Calcified tissue international. 78(4) |
| ISSN: | 0171-967X |
| Popis: | Fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) are major regulators of skeletal growth and development. Signal transduction via FGFRs is complex and mediates proliferation, differentiation, or migration depending upon the cellular context. Members of the Spry gene family antagonize the FGFR signal transduction pathway and inhibit lung morphogenesis, angiogenesis, and chondrogenesis. We examined the expression of Spry2 in the osteoblastic MC3T3-E1 cell line. MC3T3-E1 cells express Spry2 in response to FGF1 stimulation. Treatment of MC3T3-E1 cells with FGF1 results in the expression of Spry2 in a manner consistent with an early response gene. Pharmacological inhibitors of mitogen-activated protein kinase activation inhibit FGF1-induced expression of Spry2 mRNA. Transient overexpression of Spry2 in MC3T3-E1 resulted in decreased FGF1-mediated extracellular signal-regulated kinase phosphorylation and FGF1-stimulated osteopontin promoter activity. Furthermore, we show that Spry2 interacts with Raf-1 in a glutathione-S-transferase pulldown assay and that this interaction may involve multiple sites. Finally, Spry2 expression precedes the onset of the expression of osteoblast differentiation markers in an in vitro assay of primary osteoblast differentiation. Taken together, these results indicate that Spry2 expression is an early response to stimulation by FGF1 in MC3T3-E1 cells and acts as a feedback inhibitor of FGF1-induced osteoblast responses, possibly through interaction with Raf1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink