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. 2016 Mar 15;6(4):827–842.

Figure 2.

Figure 2

RTKs mediate DDR through canonical AKT and RAS pathways. In general, RTKs can activate both AKT and RAS pathways. Crosstalk between these two pathways can occur through AKT-RAF and ERK-GAB interactions. The downstream effects of the AKT pathway include inhibition of apoptosis through BAD and p27, inhibition of cell cycle progression through Chk1, downregulation of DNA damage repair through BRCA1, and indirect upregulation of DNA damage repair through ATM, ATR and DNAPK. Meanwhile, RAS itself can activate cell cycle arrest through ATR and Chk1 while promote DNA damage repair through expression of DNA ligase III, PARP1 and XRCC1. Also, the downstream of RAS pathway can activate ATM to promote DDR.