Figure 2.

Model of Spred/NF1 functional interaction based on the recent work of Stowe et al. (2012). Their work suggests that Spred1 recruits neurofibromin to the membrane via its EVH1 domain. From this location, neurofibromin dampens the activity of membrane-localized, GTP-loaded Ras via its GRD. It should be noted that it is not yet clear whether Spred1 and neurofibromin interact directly or via an intermediary protein. Moreover, a key unanswered question concerns the nature of the signals that regulate the Spred:neurofibromin interaction. For example, it is not yet clear whether this is fundamentally a mechanism of negative feedback or a way to fine-tune signaling via cross-talk from other receptors.