Figure 3. Rho GTPases in Slit/Robo signaling.

Figure 3

Rho GTPases in Slit/Robo signaling. Rho family of small GTP-binding proteins (Rho GTPases) are activated upon GTP binding and inactive when bound to GDP. Rho GTPases play an important role in the modulation of Slit function. The SH3-SH2 adaptator protein Dock, can bind directly to Robo. Dock interacts with key regulators of the actin cytoskeleton such as p21-activated protein kinase (Pak), which in turn can interact with RhoGTPases such as Rac1 and Cdc42. Slit binding to Robo increases the level of Dock-Robo association, recruits Pak and stimulates Rac. Robo also controls the activity of Rho GTPases through a family of Slit/Robo specific GAPs. SrGAP1 inactivates Cdc42 and activates RhoA but not Rac1. Slit/Robo signaling could also control Rac activity upon binding the GAP Vilse/CrossGAP. CrossGAP WW domains can directly bind to the CC2 domain of Robo. Although it inactivates Rac, Vilse seems to have a positive role in Robo repulsion.

From: Slits and Their Receptors

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