Fig. 2

Regulations in KIT protein and signaling pathway. LMTK3 directly promotes KIT protein translation, but also inhibit the expression of PKC (PKC-θ) and KIT phosphorylation. LIX1 controls MAPK pathway. Hedgehog pathway has two activate models: with ligands, HHs binding to the receptors, Patched-1/2, initiate the Hh pathway and inhibit SMO; without ligands, SMO starts to activate different GLIs, GLI1/2 up-regulate the KIT mRNA level, while GLI3 down-regulates KIT mRNA levels via the proteasome pathway. There are three classic intracellular signaling pathways for KIT activation, respectively Ras-Erk pathway, PI3K-AKT pathway and JAK-STAT pathway. Ras-Erk pathway and PI3K-AKT pathway have crosstalk with Hh pathway. FGF2 binds to and activates its receptors FGFR (FGFR3), mediating the reactivation of mutant KIT and JAK-STAT pathway. AMPD3 also promotes the JAK-STAT pathway. FGFR3 and AMPD3 both form a positive protein–protein feedback loop with mutant KIT. MiRNA-218 can inhibit JAK-STAT pathway and P55PIK can promote PI3K-AKT pathway. ACK1 activates the MAPK pathway and the PI3K pathway, whereas lix1 may only regulates the MAPK pathway