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Raf‐1 kinase inhibitor protein regulates migration of vascular smooth muscle cells independent of ERK‐MAP kinase
Author(s) -
Abraham S Thomas,
Moody Chad I,
Fenteany Gabriel
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1441
Subject(s) - cell migration , microbiology and biotechnology , vascular smooth muscle , mapk/erk pathway , cell , blot , protein kinase a , chemistry , kinase , cell culture , inhibitory postsynaptic potential , smooth muscle , biology , biochemistry , endocrinology , gene , genetics
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.