Activation of Rac1 by a Crk SH3-binding protein, DOCK180
- Etsuko Kiyokawa1,
- Yuko Hashimoto1,
- Shin Kobayashi3,
- Haruhiko Sugimura2,
- Takeshi Kurata1, and
- Michiyuki Matsuda1,3,4
- 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.
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Footnotes
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↵4 Corresponding author.
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E-MAIL mmatsuda{at}ri.imcj.go.jp; FAX 81-3-3205-1236.
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- Received April 27, 1998.
- Accepted September 1, 1998.
- Cold Spring Harbor Laboratory Press