(The FASEB Journal. 2007;21:980.1)
© 2007 FASEB
Raf-1 kinase inhibitor protein regulates migration of vascular smooth muscle cells independent of ERK-MAP kinase
S Thomas Abraham1,
Chad I Moody2 and
Gabriel Fenteany3
1 Pharmaceutical Science, Campbell University, 205 Day Dorm Rd, Science Bldg, Room 105A, Buies Creek, NC, 27506,
2 Pharmaceutical Sciences, Campbell University, 205 Day Dorm Rd, Science Bldg., Room 105A, Buies Creek, NC, 27506,
3 Chemistry, University of Connecticut, 55 North Eagleville Road, Unit 3060, Storrs, CT, 06269
ABSTRACT
Vascular smooth muscle (VSM) cell migration is a critical component in the development of atherosclerotic vascular disease. The recent characterization of raf kinase inhibitory protein (RKIP) as a mediator of epithelial cell migration prompted the investigation of a similar role in VSM cells. Locostatin (LOCO) a novel inhibitor of RKIP prevented VSM cell migration in a wound scrape culture model with an IC50 of 0.7 µM, while an inactive analog (UIC-1017) was without similar effects. At concentrations of up to 30 µM LOCO had no effect on VSM cell attachment or cell replication, and did not prevent serum-induced activation of ERK1/2. However LOCO, but not UIC, produced a rapid but transient activation of ERK1/2 in VSM cells. Western blotting experiments with RKIP antibodies revealed that VSM cells express a single immunoreactive protein of ~23kDa that is consistent with RKIP. Confocal imaging of migrating VSM cells demonstrated that RKIP was localized at the leading edge of lamellopodia. These studies provide evidence for a novel ERK-independent migration process in cultured VSM cells.
