Locostatin
Raf kinase inhibitor protein (RKIP) is a modulator of cell signaling that functions as an endogenous inhibitor of multiple kinases. Here we demonstrate a new positive role for RKIP in the regulation of cell locomotion. We discovered that RKIP is the relevant cellular target of locostatin, a novel cell migration inhibitor. Locostatin abrogates RKIP's ability to bind and inhibit Raf-1 kinase, making it the first known inhibitor of RKIP, one that acts by disrupting a protein-protein interaction, an uncommon mode of action for a small molecule. Small interfering RNA-mediated silencing of RKIP expression also reduces cell migration rate. Overexpression of RKIP converts epithelial cells to a highly migratory fibroblast-like phenotype, with dramatic reduction in the sensitivity of cells to locostatin. RKIP is therefore the compound's valid target and a key regulator of cell motility.
More on the mechanism of cell sheet migration.
More on signaling pathways to cell motility.
