The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading.

There are only three human isoforms of the small GTPase Rac, which together regulate a variety of cellular processes, including those related to actin cytoskeletal reorganization. A role for Rac3 in integrin-mediated adhesion and spreading has not been defined. We here report that CIB, a protein that binds to the ...
alpha(IIb)beta(3) fibrinogen receptor, interacts exclusively with activated (V12) Rac3 but not Rac1 or Rac2. Binding of V12Rac3 to CIB was mediated by the C-terminal end of Rac3 and by Rac3 membrane localization. Adhesion of cells on fibrinogen was accompanied by a specific increase in the levels of Rac3 but not Rac1 or Rac2 in the Triton-insoluble fraction of the cell. Also, CIB co-localized with active Rac3 to the periphery of cells adhering to fibrinogen. Expression of V12Rac3 and CIB stimulated alpha(IIb)beta(3)-mediated adhesion and spreading on fibrinogen. Moreover, adhesion through alpha(IIb)beta(3) caused a marked increase in the levels of endogenous GTP-bound Rac3 but not Rac1. These combined results strongly implicate Rac3 and CIB in integrin-associated cytoskeletal reorganization during alpha(IIb)beta(3)-mediated adhesion.
Mesh Terms:
Animals, CHO Cells, COS Cells, Carrier Proteins, Cell Adhesion, Cricetinae, Cytoskeleton, Detergents, Fibrinogen, Glutathione Transferase, Immunohistochemistry, Microscopy, Fluorescence, Nuclear Receptor Coactivator 3, Octoxynol, Plasmids, Platelet Glycoprotein GPIIb-IIIa Complex, Protein Binding, Protein Structure, Tertiary, Transcription Factors, Transfection, Two-Hybrid System Techniques, rac GTP-Binding Proteins, rac1 GTP-Binding Protein
J. Biol. Chem.
Date: Mar. 08, 2002
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