Characterization of a Novel Ras-Binding Protein Ce-FLI-1 Comprising Leucine-Rich Repeats and Gelsolin-like Domains

Ras proteins are conserved from yeasts to mammals and implicated in regulation of the actin cytoskeleton. Theflightless-1(fli-1) gene ofDrosophila melanogasterand its homologs inCaenorhabditis elegansand humans encode proteins (FLI-1) comprising a fusion of a leucine-rich repeats (LRRs) domain and a gelsolin-like domain. This LRRs domain is highly homologous to those of three proteins involved in Ras-mediated signaling;Saccharomyces cerevisiaeadenylyl cyclase,C. elegansSUR-8, and mammalian RSP-1. Here we report that the LRRs domain ofC. elegansFLI-1 (Ce-FLI-1) associates directly with Ras (Kd= 11 nM) and, when overexpressed, suppresses the heat shock sensitive phenotype of yeast cells bearing the activatedRAS2gene (RAS2Val-19). Further, the gelsolin-like domain of Ce-FLI-1 is shown to possess a Ca2+-independent G-actin-binding activity as well as F-actin-binding and -severing activities. FLI-1 may be involved in regulation of the actin cytoskeleton through Ras.