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A novel role for RhoGDI as an inhibitor of GAP proteins.
Author(s) -
Hancock J.F.,
Hall A.
Publication year - 1993
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1993.tb05840.x
Subject(s) - rhoa , biology , gtpase , gtp' , adp ribosylation factor , microbiology and biotechnology , gtpase activating protein , rac1 , rac gtp binding proteins , effector , g protein , biochemistry , signal transduction , endoplasmic reticulum , enzyme , golgi apparatus
RhoGDI inhibits guanine nucleotide dissociation from post‐translationally processed Rho and Rac proteins but its biochemical role in vivo is unknown. We show here that N‐terminal effector site mutations in the Rac protein do not compromise its interaction with RhoGDI and that, whilst geranylgeranylation and ‐AAX proteolysis of the C‐terminal CAAX motif of Rac1 and RhoA are required for efficient interaction with RhoGDI, methylesterification of the C‐terminal cysteine residue is not required. In vitro, RhoGDI can form stable complexes with Rho and Rac proteins in both the GTP and GDP bound states. Furthermore the Rac‐GTP‐‐RhoGDI complex is resistent to the action of recombinant RhoGAP and recombinant BCR. Thus GDI, by complexing with Rac‐GTP and preventing GAP stimulated GTP hydrolysis, may allow transit of the activated form of the Rac protein between physically separated activator and effector proteins in the cell.