Figure 3.

Signaling pathways regulated by asparagine or its depletion. (A) Asparagine activates mTORC1 through Arf1 or through importing other amino acids. Asparagine can also maintain mTORC1 activity during ETC inhibition. (B) Asparagine can directly bind to LCK or LKB1 to modulate their activities. As a result, asparagine is a positive regulator of TCR signaling and a negative regulator of AMPK pathway. (C) Asparagine depletion activates MAPK pathway through the induction of RTKs. MAPK activation leads to the engagement of MYC-SLC7A5 axis to support amino acid uptake, which subsequently activates mTORC1/eIF4e to support the translation of ATF4 protein.