Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1

Shinya Kuroda, Masaki Fukata, Kenta Kobayashi, Masato Nakafuku, Nobuo Nomura, Akihiro Iwamatsu, Kozo Kaibuchi

Research output: Contribution to journalArticlepeer-review

260 Citations (Scopus)

Abstract

Cdc42 and Rac1 have been implicated in the regulation of various cell functions such as cell morphology, polarity, and cell proliferation. We have partially purified a Cdc42- and Rac1-associated protein with molecular mass of about 170 kDa (p170) from bovine brain cytosol. This protein interacted with guanosine 5'-(3-O-thio)triphosphate (GTPγS).glutathione S-transferase (GST)-Cdc42 and GTPγS-GST-Rac1 but not with the GDP-GST-Cdc42, GDP-GST- Rac1, or GTPγS-GST-RhoA). We identified p170 as an IQGAP, which is originally identified as a putative Ras GTPase-activating protein. Recombinant IQGAP specifically interacted with GTPγS-Cdc42 and GTPγS-Rac1. The C-terminal fragment of IQGAP was responsible for their interactions. IQGAP was specifically immunoprecipitated with dominant-active Cdc42(val)/12 or Rac1(val)/12 from the COS7 cells expressing Cdc42(val)/12 or Rac1(val)/1, respectively. Immunofluorescence analysis revealed that IQGAP was accumulated at insulin- or Rac1-induced membrane ruffling areas. This accumulation of IQGAP was blocked by the microinjection of the dominant-negative Rac1(Asn)/17 or Cdc42(Asn)/17. Moreover, IQGAP was accumulated at the cell-cell junction in MDCK cells, where α-catenin and ZO-1 were localized. These results suggest that IQGAP is a novel target molecule for Cdc42 and Rac1.

Original languageEnglish
Pages (from-to)23363-23367
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number38
DOIs
Publication statusPublished - 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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