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Integrin-associated tyrosine kinase FAK affects Cbfa1 expression
Journal article   Peer reviewed

Integrin-associated tyrosine kinase FAK affects Cbfa1 expression

Galen B Schneider, Rebecca Zaharias, Denise Seabold and Clark Stanford
Journal of orthopaedic research, Vol.29(9), pp.1443-1447
09/2011
DOI: 10.1002/jor.21382
PMID: 21412826

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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.
Phosphorylation Calcification, Physiologic - drug effects Osteoblasts - enzymology Focal Adhesion Protein-Tyrosine Kinases - metabolism Osteoblasts - drug effects Rifabutin - analogs & derivatives Cells, Cultured Enzyme Inhibitors - pharmacology Calcification, Physiologic - physiology Rats Lactams, Macrocyclic - pharmacology RNA, Messenger - metabolism Core Binding Factor Alpha 1 Subunit - metabolism Integrins - metabolism Benzoquinones - pharmacology Gene Expression Regulation - drug effects Cell Differentiation - genetics Animals Cell Differentiation - drug effects Osteoblasts - cytology Core Binding Factor Alpha 1 Subunit - genetics Protein-Tyrosine Kinases - antagonists & inhibitors

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