FIGURE 3.

ARTN signalling. ARTN mediates the activation of the GFRα3/RET receptor complex. ARTN binds to GFRα3 which is attached to the membrane via GPI anchor. The GFRα1/RET complex has also been suggested to be a putative receptor for ARTN. Several cascades activated by GFLs via RET include the phosphorylation of MAPK (p‐ERK, p‐p38 and p‐JNK), PI3K‐AKT and Src. In addition, NCAM is an alternative signalling receptor for ARTN only in the presence of GFRα1, leading to activation of Fyn and FAK. Further, ARTN also interacts with heparan sulphate proteoglycan syndecan‐3 and mediates non‐RET signalling via activation of Src‐type kinases. Interestingly, PKA might act as regulator of upstream of RET via cAMP, or as a downstream regulator of RET