SWAP-70 is a guanine-nucleotide-exchange factor that mediates signalling of membrane ruffling

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • Masahiro Shinohara - , The University of Tokyo (Author)
  • Yoh Terada - (Author)
  • Akihiro Iwamatsu - (Author)
  • Azusa Shinohara - (Author)
  • Naoki Mochizuki - (Author)
  • Maiko Higuchi - (Author)
  • Yukiko Gotoh - (Author)
  • Sayoko Ihara - (Author)
  • Satoshi Nagata - (Author)
  • Hiroshi Itoh - (Author)
  • Yasuhisa Fukui - (Author)
  • Rolf Jessberger - , Institute of Physiological Chemistry (Author)

Abstract

Phosphoinositide-3-OH kinase (PI(3)K), activated through growth factor stimulation, generates a lipid second messenger, phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3). PtdIns(3,4,5)P3 is instrumental in signalling pathways that trigger cell activation, cytoskeletal rearrangement, survival and other reactions. However, some targets of PtdIns(3,4,5)P3 are yet to be discovered. We demonstrate that SWAP-70, a unique signalling protein, specifically binds PtdIns(3,4,5)P3. On stimulation by growth factors, cytoplasmic SWAP-70, which is dependent on PI(3)K but independent of Ras, moved to cell membrane rearrangements known as ruffles. However, mutant SWAP-70 lacking the ability to bind PtdIns(3,4,5)P3 blocked membrane ruffling induced by epidermal growth factor or platelet-derived growth factor. SWAP-70 shows low homology with Rac-guanine nucleotide exchange factors (GEFs), and catalyses PtdIns(3,4,5)P3-dependent guanine nucleotide exchange to Rac. SWAP-70-deficient fibroblasts showed impaired membrane ruffling after stimulation with epidermal growth factor, and failed to activate Rac fully. We conclude that SWAP-70 is a new type of Rac-GEF which, independently of Ras, transduces signals from tyrosine kinase receptors to Rac.

Details

Original languageEnglish
Pages (from-to)759-63
Number of pages5
JournalNature
Volume416
Issue number6882
Publication statusPublished - 18 Apr 2002
Peer-reviewedYes

External IDs

Scopus 0037129193

Keywords

Keywords

  • 3T3 Cells, Animals, Brain/drug effects, COS Cells, Cattle, Cell Membrane/drug effects, Cell Size/drug effects, Cell Surface Extensions/drug effects, Cells, Cultured, DNA-Binding Proteins/chemistry, Epidermal Growth Factor/pharmacology, Fibroblasts, Guanine Nucleotide Exchange Factors/chemistry, Humans, Mice, Minor Histocompatibility Antigens, Mutation/genetics, Nuclear Proteins/chemistry, Phosphatidylinositol Phosphates/metabolism, Platelet-Derived Growth Factor/pharmacology, Protein Binding/drug effects, Protein Transport/drug effects, Signal Transduction/drug effects, rac1 GTP-Binding Protein/antagonists & inhibitors