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Figure 9


Fig. 9. A proposed model for the involvement of Dok-4 in GDNF/RET signaling. After activation of RET by GDNF, the tyrosine at position 1062 (Y1062) in RET is autophosphorylated, which then recruits Shc or Dok4 adaptor proteins. In one pathway, phosphorylated Shc stimulates the Grb2/SOS/Ras/ERK cascade, thereby inducing transient activation of ERK. Alternatively, activation of Dok-4 leads to increased GTP-bound Rap1 levels, which induces sustained activation of ERK and neuronal differentiation including neurite outgrowth.





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