S. Kuroda et al., IDENTIFICATION OF IQGAP AS A PUTATIVE TARGET FOR THE SMALL GTPASES, CDC42 AND RAC1, The Journal of biological chemistry, 271(38), 1996, pp. 23363-23367
Cdc42 and Rac1 have been implicated in the regulation of various cell
functions such as cell morphology, polarity, and cell proliferation. W
e have partially purified a Cdc42- and Rac1-associated protein with mo
lecular mass of about 170 kDa (p170) from bovine brain cytosol. This p
rotein interacted with guanosine 5'-(3-O-thio)triphosphate (GTP gamma
S)-glutathione S-transferase (GST)-Cdc42 and GTP gamma-GST-Rac1, or GT
P gamma S-GST-RhoA). We identified p170 as an IQGAP, which is original
ly identified as putative Ras GTPase-activating protein. Recombinant I
QGAP specifically interacted with GTP gamma S-Cdc42 and GTP gamma S-Ra
c1. The C-terminal fragment of IQGAP was specifically immunoprecipitat
ed with dominant-active Cdc42(Val12) or Rac1(Val12) from the COS7 cell
s expressing Cdc42(Val12) or Rac1(Val12), respectively, Immunofluoresc
ence analysis revealed that IQGAP was accumulated at insulin- or Rac1-
induced membrane ruffling areas. This accumulation of IQGAP was blocke
d by the microinjection of the dominant-negative Rac1(Asn17) or Cdc42(
Asn17). Moreover, IQGAP was accumulated at the cell-cell junction in M
DCK cells, where alpha-catenin and ZO-1 were localized. These results
suggest that IQGAP is a novel target molecule for Cdc42 and Rac1.