Abstract
The Ezrin-Radixin-Moesin-Binding Phosphoprotein 50 (EBP50) is a scaffolding protein that regulates a variety of physiological functions. Previous studies showed that EBP50 promotes vascular smooth muscle cells (VSMC) proliferation and neointima formation following arterial injury. In this study the role of EBP50 on VSMC migration was characterized. VSMC migration was determined by wound-healing assays. The motility of primary VSMC isolated from EBP50 KO mice was significantly reduced compared to WT cells (25 um/h WT vs. 19 um/h KO, p<0.05) resulting in a 50% reduction in wound coverage. Conversely, EBP50 expression increased VSMC migration. EBP50-null VSMC had fewer and larger focal adhesions than EBP50-expressing cells. Both assembly and disassembly of focal adhesion in response to epidermal growth factor (EGF) (determined by real time TIRF microscopy) were significantly reduced in KO cells. Immunoprecipitation experiments showed that EBP50 interacts with both focal adhesion kinase (FAK) and EGF receptor (EGFR) and the formation of a complex containing both EGFR and FAK was increased by EBP50. Stimulation of VSMC with EGF induced FAK phosphorylation on Tyr925 in WT, but not in KO cell, whereas phosphorylation of Tyr397 was unaffected. Collectively, these observations indicate that EBP50 facilitates growth factors-dependent activation of FAK, and consequently, migration of VSMC. Therefore, in addition to increasing VSMC proliferation, EBP50 promotes neointima formation following arterial injury by increasing VSMC motility.
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