Unconventional Oscillations, Alternative Clocks

AKT is a protein kinase that transmits extracellular signals to regulate essential cellular processes. In mice, prior studies have shown that the active, phosphorylated form of AKT (pAKT) follows a daily rhythm, with elevated levels observed during the fed state. However, whether this rhythmic activation can be generated intrinsically independent of external cues remained unclear.

Surprisingly, we discovered that pAKT rhythms persist even in the absence of environmental time cues or a functional circadian clock, exhibiting free-running ultradian (shorter-than-24-hour) cycles of phosphorylation. Liver transcriptome analysis in clock-disrupted mice revealed matching ultradian rhythmicity in the expression of AKT-related genes and regulators, aligning with pAKT dynamics (PLOS Biology, December 30, 2021).

These findings uncover a previously unrecognized layer of temporal regulation in AKT signaling, highlighting the existence of molecular rhythms independent of the canonical circadian clock. Ongoing work in the lab aims to elucidate the underlying mechanisms and physiological significance of these clock-independent oscillations.