title: Fluoroaluminate induces pertussis toxin-sensitive protein phosphorylation: differences in MC3T3-E1 osteoblastic and NIH3T3 fibroblastic cells.
abstract: Fluoride is an acknowledged bone-forming agent that may act through stimulation of osteoblast proliferation. Fluoride's action on osteoblasts and bone is potentiated by aluminum, which can form a complex with fluoride (fluoroaluminate) and activate heterotrimeric G proteins. Here we examined signaling pathways activated by fluoroaluminate in MC3T3-E1 osteoblastic and in NIH3T3 fibroblastic cells. In MC3T3-E1 cells, fluoroaluminate induced a decrease in cAMP levels and an increase in MAP and p70 S6 kinase phosphorylations. These responses were partially or completely prevented by pertussis toxin, an inhibitor of G alpha i proteins. In NIH3T3 cells, fluoroaluminate induced weaker tyrosine and MAP kinase phosphorylations. Fluoroaluminate, but not PDGF, induced a long-lasting tyrosine phosphorylation of a 130 kDa protein only in MC3T3-E1 cells. The expression of G alpha i2, but not of G alpha s and G alpha q/11 proteins was about 10-fold higher in MC3T3-E1 cells. Thus, different signaling in osteoblastic and fibroblastic cells may be due to differential expression of G alpha i proteins and tyrosine kinase substrates and could underlie fluoride's pharmacological action in bone.
authors.affiliation: Novartis Pharma AG, Basel, Switzerland. susami1@fmi.ch
authors.forename: M
authors.initials: M
authors.lastname: Susa
authors.forename: G J
authors.initials: GJ
authors.lastname: Standke
authors.forename: M
authors.initials: M
authors.lastname: Jeschke
authors.forename: D
authors.initials: D
authors.lastname: Rohner
mesh_terms: D016475:3T3 Cells; D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005461:Fluorine / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D037342:Pertussis Toxin; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D010566:Virulence Factors, Bordetella; D005576:Colforsin; C053629:fluoroaluminum; D019000:Phosphotyrosine; D005461:Fluorine; D000535:Aluminum; D000242:Cyclic AMP; D037342:Pertussis Toxin; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases