Design principles of improving the dose-response alignment in coupled GTPase switches.

ABSTRACT: "Dose-response alignment" (DoRA), where the downstream response of cellular signaling pathways closely matches the fraction of activated receptor, can improve the fidelity of dose information transmission. The negative feedback has been experimentally identified as a key component for DoRA, but numerical simulations indicate that negative feedback is not sufficient to achieve perfect DoRA, i.e., perfect match of downstream response and receptor activation level. Thus a natural question is whether there exist design principles for signaling motifs within only negative feedback loops to improve DoRA to near-perfect DoRA. Here, we investigated several model formulations of an experimentally validated circuit that couples two molecular switches-mGTPase (monomeric GTPase) and tGTPase (heterotri

SUBMITTER: Qiao L 

PROVIDER: S-EPMC9889403 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature