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Science 289 (5482): 1194-1197

Copyright © 2000 by the American Association for the Advancement of Science

Asef, a Link Between the Tumor Suppressor APC and G-Protein Signaling

Yoshihiro Kawasaki,1 Takao Senda,2 Takao Ishidate,1 Ryo Koyama,1 Tsuyoshi Morishita,1 Yoriko Iwayama,2 Osamu Higuchi,1 Tetsu Akiyama13*

The adenomatous polyposis coli gene (APC) is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. Here the APC gene product is shown to bind through its armadillo repeat domain to a Rac-specific guanine nucleotide exchange factor (GEF), termed Asef. Endogenous APC colocalized with Asef in mouse colon epithelial cells and neuronal cells. Furthermore, APC enhanced the GEF activity of Asef and stimulated Asef-mediated cell flattening, membrane ruffling, and lamellipodia formation in MDCK cells. These results suggest that the APC-Asef complex may regulate the actin cytoskeletal network, cell morphology and migration, and neuronal function.

1 Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan.
2 Department of Anatomy I, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466, Japan.
3 Department of Oncogene Research, Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565, Japan.
*   To whom correspondence should be addressed. E-mail: akiyama{at}imcbns.iam.u-tokyo.ac.jp

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