Kinase Inhibition Leads to Hormesis in a Dual Phosphorylation-Dephosphorylation Cycle.

ABSTRACT: Many antimicrobial and anti-tumour drugs elicit hormetic responses characterised by low-dose stimulation and high-dose inhibition. While this can have profound consequences for human health, with low drug concentrations actually stimulating pathogen or tumour growth, the mechanistic understanding behind such responses is still lacking. We propose a novel, simple but general mechanism that could give rise to hormesis in systems where an inhibitor acts on an enzyme. At its core is one of the basic building blocks in intracellular signalling, the dual phosphorylation-dephosphorylation motif, found in diverse regulatory processes including control of cell proliferation and programmed cell death. Our analytically-derived conditions for observing hormesis provide clues as to why this mechanism h

SUBMITTER: Rashkov P 

PROVIDER: S-EPMC5127489 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature