Fig. 7

Model of ATP-dependent growth suppression in normal and Nf1 deficient SC. (a) Western blot from ATPγS-treated wt mSCs or (b) Nf1 −/− mSCs (1 h) with vehicle (veh; PBS) or inhibitors (Meki = PD0325901901, P2y2i = AR-C, Arrestini = barbadin, PP2i = Okadaic acid). Nf1 −/− mSCs fail to decrease pERK or pAkt in response to barbadin. (c) ATP binds to the P2y2 receptor, causing phosphorylation and recruitment of β-arrestin(s). The β-arrestin(s) form complexes; one results in the activation of Erk. A second complex contains PP2A, which de-phosphorylates Akt, correlating with growth suppression. (D) When Nf1 is inactivated ATP no longer potently suppresses SC growth. Signaling at the level of the P2Y2 receptor occurs normally, as evidenced by increased calcium on ATP stimulation. NF1−/− SC do not show the transient decrease in calcium characteristic of β-arrestin mediated suppression of G-protein-mediated signaling, or decrease phosphorylation of pThr308AKT