Rho GAP p190 Activators

Rho GAP p190 Activators comprise a set of chemical compounds that indirectly promote the activity of Rho GAP p190 by manipulating the Rho family GTPase signaling pathways. For example, Y-27632 and Fasudil, both selective inhibitors of ROCK, a downstream effector of RhoA, relieve the inhibitory phosphorylation of Rho GAP p190, thus ameliorating its GAP activity towards RhoA. Similarly, the statin family of drugs, exemplified by lovastatin, and the specific inhibitor GGTI-298, diminish prenylation of RhoA, thereby reducing its membrane association and subsequent activity, which in turn allows Rho GAP p190 to more effectively catalyze the hydrolysis of RhoA-bound GTP. Cell-permeable C3 Transferase and Exoenzyme C3 Transferase each contribute to this enhancement by ADP-ribosylating and consequently inactivating RhoA, B, and C, thus further liberating Rho GAP p190 to exert its activity. Lysophosphatidic Acid (LPA) indirectly stimulates Rho GAP p190 activity by upregulating RhoA activity, thereby increasing the cellular need for Rho GAP p190's negative regulatory function.

The balance between different Rho family GTPases is also critical in the modulation of Rho GAP p190 activity. NSC23766, by inhibiting Rac1, indirectly shifts the activity towards RhoA, potentially enhancing the regulatory role of Rho GAP p190 in controlling RhoA signaling. Conversely, ML-141 and CID-1067700 serve to obstruct the activity of Cdc42 and RhoA, respectively, which could result in a compensatory increase in RhoA activity that Rho GAP p190 would then regulate. Lastly, Ribavirin's ability to deplete cellular GTP pools results in broad suppression of Rho GTPases activities, including RhoA, which may induce a heightened functional response from Rho GAP p190. Collectively, these activators operate through diverse but interconnected biochemical mechanisms that converge on the enhancement of Rho GAP p190's role in modulating Rho GTPase signaling.