Figure 9.

Downstream effectors of RTK-mediated pathways and their biological consequences. Upon receptor tyrosine kinase (RTK) stimulation by their corresponding ligands, both PI3K/Akt/mTOR and Grb2/RAS/RAF/MEK/ERK signaling pathways can be activated in melanoma. The activation of PI3K/AKT and NRAS/RAF/MEK signaling pathways by RTKs can promote several cellular functions via the activation of MDM2, NF-κB, and CREB to enhance p53 degradation as well as promote the transcription of proliferative and anti-apoptotic genes. PI3K/AKT-induced activation of mTOR phosphorylates 4E-BP1, the inhibitor of elF-4E, to allow the release of the active form of elf-4E to initiate the translation processes of angiogenic or cell cycle gene targets. PI3K/AKT can inhibit the phosphorylation of downstream effectors, namely caspase-9, GSK-3ß, p27, and p21 to induce cell cycle progression and inhibition of apoptosis.