GDNF-, NRTN-, and ARTN-induced signaling in RMG. (A) GDNF induces phosphorylation of both MEK and ERK after 5 min, and the latter can be blocked with MEK inhibitor (U0126). Furthermore, GDNF phosphorylates SAPK/JNK after 5 min, which can be also blocked completely by U0126 and partially by PI 3-kinase inhibitor, LY294002. In addition to activating the MAPK and SAPK pathways, GDNF-induced activation of AKT/PKB was observed after 10 min of treatment, which could be also blocked by PI 3-kinase inhibitor and partially by MEK inhibitor. (B) Similar signaling cascades as described in panel A are induced by stimulation of RMG with NRTN but showing a slightly different time course: SAPK/JNK phosphorylation is observed after 10 min and AKT/PKB after only 1 min of stimulation. (C) Similar signaling cascades as described in panel A are induced by stimulation of RMG with ARTN but showing a slightly different time course: AKT/PKB after 5 min of stimulation. Equal amounts of protein were loaded under each condition as demonstrated by reincubation with antivimentin (Vim) antibody. The data shown are representative for at least three independent experiments of each stimulation set.