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

• Published in: Biochemical and biophysical research communications Vol. 257; no. 1; pp. 111 - 116
• Main Authors: Goshima, Masahiro, Kariya, Ken-ichi, Yamawaki-Kataoka, Yuriko, Okada, Tomoyo, Shibatohge, Mitsushige, Shima, Fumi, Fujimoto, Etsuko, Kataoka, Tohru
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02-04-1999
• Subjects: Actins - metabolism; Actins - ultrastructure; Adenylyl Cyclases - metabolism; Animals; Binding, Competitive; Caenorhabditis elegans - chemistry; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Calcium - metabolism; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Dose-Response Relationship, Drug; Drosophila Proteins; Egtazic Acid - pharmacology; Enzyme Activation - drug effects; Gelsolin - chemistry; Gelsolin - genetics; Heat-Shock Response; Helminth Proteins - chemistry; Helminth Proteins - genetics; Helminth Proteins - metabolism; Humans; Insect Proteins - chemistry; Insect Proteins - genetics; Insect Proteins - metabolism; Leucine - chemistry; Leucine - genetics; Oncogene Protein p21(ras) - antagonists & inhibitors; Oncogene Protein p21(ras) - metabolism; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Protein Binding - drug effects; Protein Biosynthesis; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Sequence Homology, Amino Acid
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.0420

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.