Figure 1.9.

Interaction of MAPKs with clock proteins. MAPKs from different families can directly influence clock proteins in the molecular oscillator. ERK MAPK physically interacts with and phosphorylates CLOCK and BMAL1 in the positive branch of the oscillator and CRY1 and CRY2 in the negative branch. No physical interactions of p38 with clock proteins have been observed, and no p38-specific phosphorylation sites have been identified on clock proteins. However, inhibition of p38 led to a longer period of clock gene oscillation, implying that p38 may have an unknown effect on the molecular oscillator. Finally, JNK MAPK interacts with and phosphorylates BMAL1 and PER2.