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. 2024 Feb 11;13(4):333. doi: 10.3390/cells13040333

Figure 3.

Figure 3

Examples for regulation of DLK activity. (A) Under basal unstimulated conditions, unphosphorylated DLK protein abundance is regulated by the E3 ubiquitin ligase PHR1 and the deubiquitinase USP9X. (B) Signals activating cAMP and PKA phosphorylate dimerized DLK on Ser-302, leading to the activation of MKK4/7 and JNK. JNK, in turn, phosphorylates DLK on Thr-43 and Ser-535, preventing the interaction with PHR1, thereby stabilizing DLK. Other signals activating MAP4K phosphorylate DLK on Thr-43 and stabilize DLK. (C) Upon an increase in the intracellular calcium concentration, calcineurin interacts with monomeric or dimeric DLK and dephosphorylates the kinase. The inhibition of calcineurin by ROS prevents the dephosphorylation of DLK, whereas the interaction of immunophilin-bound CsA or FK506 displaces DLK from the calcineurin interaction site, and DLK dimerizes and autophosphorylates in trans. For further information, please see the text.