GDIs block activation of Rho GTPase:GDP

Stable Identifier
R-HSA-194854
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Reaction
Species
Homo sapiens
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GDP dissociation inhibitors or GDIs confer an additional but important layer of Rho GTPase regulation along with GEFs and GAPs. GDIs mainly inhibit the dissociation of bound guanine nucleotide (usually GDP) from their partner GTPases. So far, three human GDIs with proven biological functions have been found: RhoGDI/GDIalpha/GDI1, hematopoietic cell selective Ly/D4GDI/GDIbeta/GDI2, and Rho GDIgamma/GDI3 (DerMardirossian and Bokoch, 2005). Three specific biochemical functions of GDIs have been established: inhibiting the dissociation of GDP from Rho proteins, maintaining the GTPases in an inactive form, and preventing GTPase activation by GEFs (Olofsson, 1999).

Literature References
PubMed ID Title Journal Year
1439791 A GDP dissociation inhibitor that serves as a GTPase inhibitor for the Ras-like protein CDC42Hs

Hart, MJ, Maru, Y, Leonard, D, Witte, ON, Evans, T, Cerione, RA

Science 1992
9194563 C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases

Gosser, YQ, Nomanbhoy, TK, Aghazadeh, B, Manor, D, Combs, C, Cerione, RA, Rosen, MK

Nature 1997
10655614 The Rac-RhoGDI complex and the structural basis for the regulation of Rho proteins by RhoGDI

Scheffzek, K, Stephan, I, Jensen, ON, Illenberger, D, Gierschik, P

Nat Struct Biol 2000
9113980 RhoGDIgamma: a GDP-dissociation inhibitor for Rho proteins with preferential expression in brain and pancreas

Adra, CN, Manor, D, Ko, JL, Zhu, S, Horiuchi, T, Van Aelst, L, Cerione, RA, Lim, B

Proc Natl Acad Sci U S A 1997
15921909 GDIs: central regulatory molecules in Rho GTPase activation

DerMardirossian, C, Bokoch, GM

Trends Cell Biol 2005
10676816 Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI

Hoffman, GR, Nassar, N, Cerione, RA

Cell 2000
15292224 ExoS Rho GTPase-activating protein activity stimulates reorganization of the actin cytoskeleton through Rho GTPase guanine nucleotide disassociation inhibitor

Sun, J, Barbieri, JT

J Biol Chem 2004
7543319 Expression patterns of two human genes coding for different rab GDP-dissociation inhibitors (GDIs), extremely conserved proteins involved in cellular transport

Bachner, D, Sedlacek, Z, Korn, B, Hameister, H, Poustka, A

Hum Mol Genet 1995
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