Kiyokawa E, Hashimoto Y, Kobayashi S, Sugimura H, Kurata T, Matsuda M
Department of Pathology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Genes Dev. 1998 Nov 1;12(21):3331-6. doi: 10.1101/gad.12.21.3331.
DOCK180 is involved in integrin signaling through CrkII-p130(Cas) 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 p130(Cas) 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.
DOCK180通过CrkII-p130（Cas）复合物参与整合素信号传导。我们研究了DOCK180在Rac1信号级联反应中的作用。DOCK180以依赖于Rac1、Cdc42Hs和SEK的方式激活JNK，并且DOCK180的过表达增加了293T细胞中结合GTP的Rac1的量。CrkII和p130（Cas）的共表达增强了这种DOCK180依赖性的Rac1激活。此外，我们观察到DOCK180与Rac1直接结合，但不与RhoA或Cdc42Hs结合。显性负性Rac1抑制DOCK180诱导的膜伸展。这些结果强烈表明DOCK180是Rac1的一种新型激活剂，并参与整合素信号传导。
