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

Author

Listed:
  • Masahiro Shinohara

    (University of Tokyo)

  • Yoh Terada

    (University of Tokyo
    Yamanouchi Pharmaceutical Co. Ltd)

  • Akihiro Iwamatsu

    (Kirin Brewery)

  • Azusa Shinohara

    (Kirin Brewery)

  • Naoki Mochizuki

    (International Medical Center of Japan
    National Cardiovascular Center Research Institute)

  • Maiko Higuchi

    (University of Tokyo)

  • Yukiko Gotoh

    (University of Tokyo)

  • Sayoko Ihara

    (University of Tokyo)

  • Satoshi Nagata

    (University of Tokyo
    National Cancer Institute, National Institute of Health)

  • Hiroshi Itoh

    (University of Tokyo)

  • Yasuhisa Fukui

    (University of Tokyo)

  • Rolf Jessberger

    (The Carl C. Icahn Institute for Gene Therapy and Molecular Medicine)

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)1,2,3,4,5. PtdIns(3,4,5)P3 is instrumantal 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 discovered1,2,3,4,5,6,7. We demonstrate that SWAP-70, a unique signalling protein8,9,10, 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.

Suggested Citation

  • Masahiro Shinohara & Yoh Terada & Akihiro Iwamatsu & Azusa Shinohara & Naoki Mochizuki & Maiko Higuchi & Yukiko Gotoh & Sayoko Ihara & Satoshi Nagata & Hiroshi Itoh & Yasuhisa Fukui & Rolf Jessberger, 2002. "SWAP-70 is a guanine-nucleotide-exchange factor that mediates signalling of membrane ruffling," Nature, Nature, vol. 416(6882), pages 759-763, April.
    • Handle: RePEc:nat:nature:v:416:y:2002:i:6882:d:10.1038_416759a
    DOI: 10.1038/416759a
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