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. 2021 Jun 9;11(6):860. doi: 10.3390/biom11060860

Figure 5.

Figure 5

A schematic illustration of signaling mechanism in GDNF-induced human medullary thyroid cancer cell proliferation. GDNF activates RET protein. Activation of RET causes phosphorylation of ERK1/2 and subsequent activation of EGR1. Active EGR1 causes nuclear accumulation of p35 that can binding and activates CDK5. Active CDK5 physically interacts with the intracellular domain of RET protein to pass through the GDNF-activated signaling cascade. Finally, CDK5 activates STAT3 by its specific phosphorylation on Ser727. This further trigger medullary thyroid cancer cell proliferation.