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 regulat ion of the actin cytoskeleton. The flightless-1 (fli-1) gene of Drosophila melanogaster and its homologs in Caenorhabditis elegans and humans encode p roteins (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 cerevi siae adenylyl cyclase, C. elegans SUR-8, and mammalian RSP-1. Here we repor t that the LRRs domain of C. elegans FLI-1 (Ce-FLI-1) associates directly w ith Has (K-d = 11 nM) and, when overexpressed, suppresses the heat shock se nsitive phenotype of yeast cells bearing the activated RAS2 gene (RAS2(Val- 19)). Further, the gelsolin-like domain of Ce-FLI-1 is shown to possess a C a2+-independent G-actin-binding activity as well as F-actin-binding and -se vering activities. FLI-1 may be involved in regulation of the actin cytoske leton through Has. (C) 1999 Academic Press.