title: Integrin-associated tyrosine kinase FAK affects Cbfa1 expression.
abstract: Following cell adhesion, focal adhesion kinase (FAK) autophosphorylates on tyrosine and regulates intracellular signaling cascades that regulate cell growth and differentiation. The hypothesis of this study was FAK mediates osteoblast differentiation dependent Cbfa1 expression. Slowly mineralizing UI and rapidly mineralizing UMR-106-01 BSP osteoblasts formed focal adhesions; however, the level of FAK in UI focal adhesions was less than that seen in BSP cells. UI cultures had less FAK expression (p < 0.05) along with elevated levels of FAK phosphotyrosine in comparison to rapidly mineralizing BSP cultures. Mineralization decreased in a dose-dependent manner in response to Herbimycin A, a tyrosine kinase inhibitor. Overexpression of FAK in UI cells led to a fourfold increase in Cbfa1 gene expression (p < 0.02), and an increase in Cbfa1 protein expression. These results suggest that the integrin-associated tyrosine kinase FAK contributes to the regulation of the osteoblast differentiation in part through the regulation of Cbfa1 expression.
authors.affiliation: Department of Prosthodontics, University of Iowa College of Dentistry, The University of Iowa, Iowa City, Iowa 52242-1001, USA. galen-schneider@uiowa.edu
authors.forename: Galen B
authors.initials: GB
authors.lastname: Schneider
authors.forename: Rebecca
authors.initials: R
authors.lastname: Zaharias
authors.forename: Denise
authors.initials: D
authors.lastname: Seabold
authors.forename: Clark
authors.initials: C
authors.lastname: Stanford
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D016023:Integrins / Q000378:metabolism*; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017828:Rifabutin / Q000031:analogs & derivatives
chemical_list: D016227:Benzoquinones; D050659:Core Binding Factor Alpha 1 Subunit; D004791:Enzyme Inhibitors; D016023:Integrins; D047029:Lactams, Macrocyclic; D012333:RNA, Messenger; C493717:Runx2 protein, rat; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases