Rho GTPase cycle

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Homo sapiens
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The cycling of Rho GTPases is tightly controlled by three classes of protein. These are (1) guanine nucleotide dissociation inhibitors or GDIs, which maintain Rho proteins in an inactive state in the cytoplasm, (2) guanine nucleotide exchange factors or GEFs, which destabilize the interaction between Rho proteins and their bound nucleotide, the net result of which is the exchange of bound GDP for the more abundant GTP, and (3) GTPase Activating Proteins or GAPs, which stimulate the low intrinsic GTP hydrolysis activity of Rho family members, thus promoting their inactivation. GDIs, GEFs, and GAPs are themselves subject to tight regulation, and the overall level of Rho activity reflects the balance of their activities.

In their active GTP-bound state, Rho family members have the ability to interact with a large variety of so-called effector proteins. By changing the subcellular localization of effectors, by altering their enzymatic properties, or by directing the formation of specific effector complexes, members of the Rho family mediate their various effects.

This Rho GTPase cycle is diagrammed in the figure below. External or internal cues promote the release of Rho GTPases from the inhibitory complex, which allows them to associate with the plasma membrane, where they are activated by GEFs (1) and can signal to effector proteins (4). Then, GAPs inactivate the GTPases by accelerating the intrinsic GTPase activity, leading to the GDP bound form (2). Once again, the GDI molecules stabilize the inactive GDP bound form in the cytoplasm, waiting for further instructions (3). For review, please refer to Van Aelst and D'Souza-Schorey 1997, Jaffe and Hall 2005, Tcherkezian and Lamarche Vane 2007).

Literature References
PubMed ID Title Journal Year
9308960 Rho GTPases and signaling networks

Van Aelst, L, D'Souza-Schorey, C

Genes Dev 1997
17222083 Current knowledge of the large RhoGAP family of proteins

Tcherkezian, J, Lamarche-Vane, N

Biol Cell 2007
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