A novel role for RhoGDI as an inhibitor of GAP proteins.

AUTOR(ES)

Hancock, J F

RESUMO

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.

Documentos Relacionados

• Rho guanine nucleotide dissociation inhibitor protein (RhoGDI) inhibits exocytosis in mast cells.
• RhoGDI: multiple functions in the regulation of Rho family GTPase activities
• Defects in cytokinesis, actin reorganization and the contractile vacuole in cells deficient in RhoGDI
• Mannosamine, a novel inhibitor of glycosylphosphatidylinositol incorporation into proteins.
• Bovine pancreatic trypsin inhibitor-trypsin complex as a detection system for recombinant proteins.