Interaction of Rac1 with GTPase-activating proteins and putative effectors. A comparison with Cdc42 and RhoA.

The Journal of Biological Chemistry
B ZhangY Zheng

Abstract

The intrinsic GTPase activity of the Rho family GTP-binding protein Rac1 is drastically stimulated upon interaction with its GTPase-activating proteins (GAPs) and is significantly inhibited when coupled to certain effector targets such as the p21-activated kinases (PAKs) and IQGAPs. Here we have characterized the interaction of Rac1 with a panel of mammalian GAPs and putative effectors by measuring the kinetic and binding parameters involved and made comparisons with similar interactions for Cdc42 and RhoA. In contrast with Cdc42 (for which the GAP domain of p50RhoGAP is 50-fold more efficient than those of p190, Bcr, and 3BP-1) and with RhoA (toward which only p50RhoGAP and p190 displayed high efficiencies), the catalytic efficiencies (Kcat/Km) of the GAP domains of p50RhoGAP, p190, Bcr, and 3BP-1 on Rac1 are found to be comparable in a range between 0.9 and 2.6 min-1 microM-1. However, similar to the cases of Cdc42 and RhoA, the Km values of the GAP domains on Rac1 compare well to the binding affinity to the guanylyl imidodiphosphate-bound Rac1, which ranges from 10.5 to 40.5 microM, suggesting a rapid equilibrium reaction mechanism. The dissociation constants of the p21-binding domains of PAK1, PAK2, and the RasGAP-related d...Continue Reading

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