Cdc42 and Rac1 regulate the interaction of IQGAP1 with β-catenin

Masaki Fukata, Shinya Kuroda, Masato Nakagawa, Aie Kawajiri, Naohiro Itoh, Ikuo Shoji, Yoshiharu Matsuura, Shin Yonehara, Hajime Fujisawa, Akira Kikuchi, Kozo Kaibuchi

Research output: Contribution to journalArticlepeer-review

172 Citations (Scopus)

Abstract

IQGAP1, a target of Cdc42 and Rac1 small GTPases, directly interacts with β-catenin and negatively regulates E-cadherin-mediated cell-cell adhesion by dissociating α-catenin from the cadherin-catenin complex in vivo (Kuroda, S., Fukata, M., Nakagawa, M., Fujii, K., Nakamura, T., Ookubo, T., Izawa, L., Nagase, T., Nomura, N., Tani, H., Shoji, L., Matsuura, Y., Yonehara, S., and Kaibuchi, K. (1998) Science 281, 832-835). Here we investigated how Cdc42 and Rac1 regulate the IQGAP1 function. IQGAP1 interacted with the amino-terminal region (amino acids 1-183) of β-catenin, which contains the α-catenin-binding domain. IQGAP1 dissociated α-catenin from the β-catenin-α-catenin complex in a dose-dependent manner in vitro. Guanosine 5'-(3-O-thio)triphosphate (GTPγS)·glutathione S-transferase (GST)Cdc42 and GTPγS·GST-Rac1 inhibited the binding of IQGAP1 to β-catenin in a dose-dependent manner in vitro, whereas neither GDP·GST-Cdc42, GDP·GST-Rac1, nor GTPγS·GST-RhoA did. The coexpression of dominant active Cdc42 with IQGAP1 suppressed the dissociation of α-catenin from the cadherin-catenin complex induced by the overexpression of IQGAP1 in L cells expressing E-cadherin (EL cells). Consistent with this, the overexpression of either dominant negative Cdc42 or Rac1 resulted in the reduction of E- cadherin-mediated cell adhesive activity in EL cells. These results indicate that Cdc42 and Rac1 negatively regulate the IQGAP1 function by inhibiting the interaction of IQGAP1 with β-catenin, leading to stabilization of the cadherin-catenin complex.

Original languageEnglish
Pages (from-to)26044-26050
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number37
DOIs
Publication statusPublished - 10-09-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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