Activation of Rac1 by a Crk SH3-binding protein, DOCK180

  1. Etsuko Kiyokawa1,
  2. Yuko Hashimoto1,
  3. Shin Kobayashi3,
  4. Haruhiko Sugimura2,
  5. Takeshi Kurata1, and
  6. Michiyuki Matsuda1,3,4
  1. 1Department of Pathology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; 2First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan; 3Department of Pathology, Research Institute, International Medical Center of Japan, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan

Abstract

DOCK180 is involved in integrin signaling through CrkII-p130Cas complexes. We have studied the involvement of DOCK180 in Rac1 signaling cascades. DOCK180 activated JNK in a manner dependent on Rac1, Cdc42Hs, and SEK, and overexpression of DOCK180 increased the amount of GTP-bound Rac1 in 293T cells. Coexpression of CrkII and p130Cas enhanced this DOCK180-dependent activation of Rac1. Furthermore, we observed direct binding of DOCK180 to Rac1, but not to RhoA or Cdc42Hs. Dominant-negative Rac1 suppressed DOCK180-induced membrane spreading. These results strongly suggest that DOCK180 is a novel activator of Rac1 and involved in integrin signaling.

Keywords

Footnotes

  • 4 Corresponding author.

  • E-MAIL mmatsuda{at}ri.imcj.go.jp; FAX 81-3-3205-1236.

    • Received April 27, 1998.
    • Accepted September 1, 1998.
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