Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution.

ABSTRACT: The Ras-superfamily GTPases are central controllers of cell proliferation and morphology. Ras signaling is mediated by a system of interacting molecules: upstream enzymes (GEF/GAP) regulate Ras's ability to recruit multiple competing downstream effectors. We developed a multiplexed, multi-turnover assay for measuring the dynamic signaling behavior of in vitro reconstituted H-Ras signaling systems. By including both upstream regulators and downstream effectors, we can systematically map how different network configurations shape the dynamic system response. The concentration and identity of both upstream and downstream signaling components strongly impacted the timing, duration, shape, and amplitude of effector outputs. The distorted output of oncogenic alleles of Ras was highly dependent o

SUBMITTER: Coyle SM 

PROVIDER: S-EPMC4775219 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature