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Fig. 2. Non-Ret signalling for GDNF and GFR{alpha}-independent signalling for RET. (A) GDNF promotes phosphorylation of Met. Its activation is indirect and is mediated by Src-type kinases. Various types of evidence suggest that GDNF is locally concentrated by heparan sulphate proteoglycans, such as syndecan. By contrast, RET is phosphorylated, by an unknown mechanism, through the activation of TrkA. Heparan sulphate proteoglycans may modulate GDNF signalling by local concentration of the ligand. (B) NCAM is an alternative signalling receptor for GFLs. It interacts with a GDNF-GFR{alpha} dimer leading to activation of Fyn, a Src-like kinase, for instance. It is not known whether Fyn activates Met in NCAM-mediated GDNF signalling.