IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs

EMBO J. 1996 Jun 17;15(12):2997-3005.


Proteins that associate with the GTP-bound forms of the Ras superfamily of proteins are potential effector targets for these molecular switches. A 195 kDa protein was purified from cell lysates by affinity chromatography on immobilized cdc42Hs-GTP and a corresponding cDNA was isolated. Sequence analysis revealed localized identities to calponin, the WW domain, unconventional myosins and to the rasGAP-related domain (GRD) contained in IRA, NF-1, SAR1 and rasGAP. p195 was found to be identical to IQGAP1, a protein previously reported to bind ras. Purified recombinant p195/IQGAP1 bound to and inhibited the GTPase activity of cdc42Hs and rac whereas no interaction with ras was detected. The C-terminal half of IQGAP1 containing the GRD bound to cdc42 and rac in a GRD-dependent fashion, but a smaller fragment containing only the GRD did not. Cdc42 was also co-immunoprecipitated from cell lysates with antibody specific to p195/IQGAP1. Calmodulin also co-immunoprecipitated with p195/IQGAP1 and was found to associate with fragments containing the IQ domain. Expression of a cDNA fragment encoding the GRD inhibited the CDC24/CDC42 pathway in yeast, but no effect on ras was observed. In mammalian cells, both endogenous and ectopically expressed p195/IQGAP1 were localized to lamellipodia and ruffling cell membranes, where co-localization with actin was apparent. These results suggest that IQGAP1 is an effector target for cdc42Hs and may mediate the effects of this GTPase on cell morphology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calmodulin / metabolism*
  • Calmodulin-Binding Proteins / genetics
  • Calmodulin-Binding Proteins / isolation & purification
  • Calmodulin-Binding Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Chromatography, Affinity
  • Cloning, Molecular
  • DNA, Complementary
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / metabolism*
  • Immunohistochemistry
  • Molecular Sequence Data
  • Protein Binding
  • Sequence Homology, Amino Acid
  • cdc42 GTP-Binding Protein
  • ras GTPase-Activating Proteins*


  • Calmodulin
  • Calmodulin-Binding Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA, Complementary
  • IQ motif containing GTPase activating protein 1
  • ras GTPase-Activating Proteins
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • cdc42 GTP-Binding Protein