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Science 7 August 1998:
Vol. 281. no. 5378, pp. 832 - 835
DOI: 10.1126/science.281.5378.832
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Reports

Role of IQGAP1, a Target of the Small GTPases Cdc42 and Rac1, in Regulation of E-Cadherin- Mediated Cell-Cell Adhesion

Shinya Kuroda, Masaki Fukata, Masato Nakagawa, Katsuhiko Fujii, Tomoko Nakamura, Tadashi Ookubo, Ichiro Izawa, Takahiro Nagase, Nobuo Nomura, Hideki Tani, Ikuo Shoji, Yoshiharu Matsuura, Shin Yonehara, Kozo Kaibuchi *

The small guanosine triphosphatases (GTPases) Cdc42 and Rac1 regulate E-cadherin-mediated cell-cell adhesion. IQGAP1, a target of Cdc42 and Rac1, was localized with E-cadherin and beta -catenin at sites of cell-cell contact in mouse L fibroblasts expressing E-cadherin (EL cells), and interacted with E-cadherin and beta -catenin both in vivo and in vitro. IQGAP1 induced the dissociation of alpha -catenin from a cadherin-catenin complex in vitro and in vivo. Overexpression of IQGAP1 in EL cells, but not in L cells expressing an E-cadherin-alpha -catenin chimeric protein, resulted in a decrease in E-cadherin-mediated cell-cell adhesive activity. Thus, IQGAP1, acting downstream of Cdc42 and Rac1, appears to regulate cell-cell adhesion through the cadherin-catenin pathway.

S. Kuroda, Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630-0101, Japan, and Inheritance and Variation Group, PRESTO, Japan Science and Technology, Kyoto 619-0237, Japan. M. Fukata, Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630-0101, Japan, and Department of Biochemistry, Hiroshima University School of Medicine, Hiroshima 734-8551, Japan. M. Nakagawa, K. Fujii, T. Nakamura, T. Ookubo, K. Kaibuchi, Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630-0101, Japan. I. Izawa, Central Laboratories for Key Technology, Kirin Brewery, Yokohama 236-0004, Japan. T. Nagase and N. Nomura, Kazusa cDNA Research Group, Kazusa DNA Research Institute, Kisarazu 292-0812, Japan. H. Tani, I. Shoji, Y. Matsuura, Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-0052, Japan. S. Yonehara, Institute for Virus Research, Kyoto University, Kyoto 606-8397, Japan.
*   To whom correspondence should be addressed.

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J. M. Mei, N. G. Hord, D. F. Winterstein, S. P. Donald, and J. M. Phang (2000)
Cancer Res. 60, 3379-3383
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Expression of prostaglandin endoperoxide H synthase-2 induced by nitric oxide in conditionally immortalized murine colonic epithelial cells.
J. M. MEI, N. G. HORD, D. F. WINTERSTEIN, S. P. DONALD, and J. M. PHANG (2000)
FASEB J 14, 1188-1201
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Oncogenic Ras Downregulates Rac Activity, Which Leads to Increased Rho Activity and Epithelial-Mesenchymal Transition.
G. C.M. Zondag, E. E. Evers, J. P. ten Klooster, L. Janssen, R. A. van der Kammen, and J. G. Collard (2000)
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Regulation of Cadherin Adhesive Activity.
B. M. Gumbiner (2000)
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Gastric Hyperplasia in Mice Lacking the Putative Cdc42 Effector IQGAP1.
S. Li, Q. Wang, A. Chakladar, R. T. Bronson, and A. Bernards (2000)
Mol. Cell. Biol. 20, 697-701
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Plakoglobin and beta-catenin: protein interactions, regulation and biological roles.
J Zhurinsky, M Shtutman, and A Ben-Ze'ev (2000)
J. Cell Sci. 113, 3127-3139
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IQGAP1 and Calmodulin Modulate E-cadherin Function.
Z. Li, S. H. Kim, J. M. G. Higgins, M. B. Brenner, and D. B. Sacks (1999)
J. Biol. Chem. 274, 37885-37892
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Establishment of the Circumferential Actin Filament Network Is a Prerequisite for Localization of the Cadherin-Catenin Complex in Epithelial Cells.
M. P. Quinlan and J. L. Hyatt (1999)
Cell Growth Differ. 10, 839-854
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Tyrosine Phosphorylation of the Bcl-2-associated Protein BNIP-2 by Fibroblast Growth Factor Receptor-1 Prevents Its Binding to Cdc42GAP and Cdc42.
B. C. Low, Y. P. Lim, J. Lim, E. S. M. Wong, and G. R. Guy (1999)
J. Biol. Chem. 274, 33123-33130
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Localization of the PAK1-, WASP-, and IQGAP1-specifying Regions of Cdc42.
R. Li, B. Debreceni, B. Jia, Y. Gao, G. Tigyi, and Y. Zheng (1999)
J. Biol. Chem. 274, 29648-29654
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Cdc42 and Rac1 Regulate the Interaction of IQGAP1 with beta -Catenin.
M. Fukata, S. Kuroda, M. Nakagawa, A. Kawajiri, N. Itoh, I. Shoji, Y. Matsuura, S. Yonehara, H. Fujisawa, A. Kikuchi, et al. (1999)
J. Biol. Chem. 274, 26044-26050
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Regulated CD44 Cleavage under the Control of Protein Kinase C, Calcium Influx, and the Rho Family of Small G Proteins.
I. Okamoto, Y. Kawano, M. Matsumoto, M. Suga, K. Kaibuchi, M. Ando, and H. Saya (1999)
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Phosphorylation of Adducin by Rho-Kinase Plays a Crucial Role in Cell Motility.
Y. Fukata, N. Oshiro, N. Kinoshita, Y. Kawano, Y. Matsuoka, V. Bennett, Y. Matsuura, and K. Kaibuchi (1999)
J. Cell Biol. 145, 347-361
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The Cadherin-Catenin System: Implications for Growth and Differentiation of Endocrine Tissues.
E. Pötter, C. Bergwitz, and G. Brabant (1999)
Endocr. Rev. 20, 207-239
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