In addition to regulating Rho family proteins, the EPH receptors and ephrins (EFNs) also regulate the activity of Ras family proteins. Ras-MAPK pathway is a key regulator of cell proliferation, adhesion and transformation, but can also influence axon guidance (Forcet et al. 2002). EPHB receptors downregulate H-Ras and consequently its downstream effector extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway in neuronal cells (Elowe et al. 2001, Miao et al. 2000). EPHB2 signals through the SH2 domain protein p120-RasGAP (RASA1) to inhibit the Ras-MAPK pathway. p120-RasGAP binds directly through its SH2 domains to the autophosphorylated EPHB2 juxtamembrane region (Holland et al. 1997, Elowe et al. 2001).