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Regulation of RhoA GTP Hydrolysis by the GTPase-Activating Proteins p190, p50RhoGAP, Bcr, and 3BP-1
Abstract
The small GTP-binding protein RhoA becomes inactivated by hydrolyzing bound GTP to GDP through its intrinsic GTPase activity which is further stimulated by a family of Rho GTPase-activating proteins (GAPs). Here we have compared the kinetics of interaction between recombinant RhoA and the RhoGAP domains of p190, p50RhoGAP, Bcr, and 3BP-1. The intrinsic rate of GTP hydrolysis by RhoA is relatively slow when compared to other Rho-family GTPases such as Cdc42 or Rac1 with a rate constant of 0.022 min-1, which can be further stimulated at least 4000-fold by p190 or p50RhoGAP. The RhoGAP domains of Bcr and 3BP-1, which were thought to be inactive toward RhoA, are also found capable of stimulating the GTPase activity of RhoA in a dose-dependent manner. The supreme catalytic activities of p190 and p50RhoGAP toward RhoA reside mostly in their lower Km values (1.79 and 2.83 microM, respectively) which correlate well with their binding affinity for GMP-PNP-bound RhoA (2.18 and 2. 47 microM, respectively), in contrast with Bcr and 3BP-1 which interact with the activated RhoA with much higher Km (89 microM). However, the mechanisms of catalysis by p190 and p50RhoGAP are distinct in at least three aspects: (1) p50RhoGAP displays an effect of product inhibition by binding to the GDP-bound form of RhoA with a Kd of 6 microM in comparison with the Kd for p190 of 33 microM; (2) the Km of p190 increases drastically upon the increase of salt and Mg2+ concentrations, conditions under which only…
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“we tested Rho GAP p50, a potent GAP for RhoA, Rac, and CDC42.”
From The Hematopoiesis-Specific GTP-Binding Protein RhoH Is GTPase Deficient and Modulates Activities of Other Rho GTPases by an Inhibitory Function (2002) · cites this paper as [63]
In the citing paper
“About 20 GAPs for Rho GTPases have been identified to date (8, 31, 63).”
From The Hematopoiesis-Specific GTP-Binding Protein RhoH Is GTPase Deficient and Modulates Activities of Other Rho GTPases by an Inhibitory Function (2002) · cites this paper as [63]
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Self-citation
Metadata
- Authors
- Zhang, B., & Zheng, Y.
- Affiliations
- Department of Biochemistry, University of Tennessee, Memphis, Tennessee 38163
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 1998-03-24
- Volume
- 37
- Issue
- 15
- Pages
- 5249-5257
- ISSN
- 0006-2960
- 1520-4995
- Cited by
- 75
- References
- 14
- Language
- en
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- CoChat. (2026). Citation check: Regulation of RhoA GTP Hydrolysis by the GTPase-Activating Proteins p190, p50RhoGAP, Bcr, and 3BP-1. https://app.cochat.ai/papers/10.1021/bi9718447
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