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Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization

Author

Listed:
  • Neng Yang

    (Faculty of Science, Kyushu University)

  • Osamu Higuchi

    (Faculty of Science, Kyushu University)

  • Kazumasa Ohashi

    (Faculty of Science, Kyushu University)

  • Kyoko Nagata

    (Faculty of Science, Kyushu University)

  • Atsushi Wada

    (Graduate School of Science, Kyoto University)

  • Kenji Kangawa

    (National Cardiovascular Center Research Institute)

  • Eisuke Nishida

    (Graduate School of Science, Kyoto University)

  • Kensaku Mizuno

    (Faculty of Science, Kyushu University
    Inheritance and Variation, PRESTO, Japan Science and Technology Corporation)

Abstract

Rac is a small GTPase of the Rho family that mediates stimulus-induced actin cytoskeletal reorganization to generate lamellipodia1,2,3,4,5. Little is known about the signalling pathways that link Rac activation to changes in actin filament dynamics. Cofilin is known to be a potent regulator of actin filament dynamics6,7,8,9,10, and its ability to bind and depolymerize actin is abolished by phosphorylation of serine residue at 3 (refs 11, 12); however, the kinases responsible for this phosphorylation have not been identified. Here we show that LIM-kinase 1 (LIMK-1), a serine/threonine kinase containing LIM and PDZ domains13,14,15,16, phosphorylates cofilin at Ser 3, both in vitro and in vivo. When expressed in cultured cells, LIMK-1 induces actin reorganization and reverses cofilin-induced actin depolymerization. Expression of an inactive form of LIMK-1 suppresses lamellipodium formation induced by Rac or insulin. Furthermore, insulin and an active form of Rac increase the activity of LIMK-1. Taken together, our results indicate that LIMK-1 participates in Rac-mediated actin cytoskeletal reorganization, probably by phosphorylating cofilin.

Suggested Citation

  • Neng Yang & Osamu Higuchi & Kazumasa Ohashi & Kyoko Nagata & Atsushi Wada & Kenji Kangawa & Eisuke Nishida & Kensaku Mizuno, 1998. "Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization," Nature, Nature, vol. 393(6687), pages 809-812, June.
    • Handle: RePEc:nat:nature:v:393:y:1998:i:6687:d:10.1038_31735
    DOI: 10.1038/31735
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