Sensitivity analysis of intracellular signaling pathway kinetics predicts targets for stem cell fate control.

ABSTRACT: Directing stem cell fate requires knowledge of how signaling networks integrate temporally and spatially segregated stimuli. We developed and validated a computational model of signal transducer and activator of transcription-3 (Stat3) pathway kinetics, a signaling network involved in embryonic stem cell (ESC) self-renewal. Our analysis identified novel pathway responses; for example, overexpression of the receptor glycoprotein-130 results in reduced pathway activation and increased ESC differentiation. We used a systematic in silico screen to identify novel targets and protein interactions involved in Stat3 activation. Our analysis demonstrates that signaling activation and desensitization (the inability to respond to ligand restimulation) is regulated by balancing the activation state of

SUBMITTER: Mahdavi A 

PROVIDER: S-EPMC1913098 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature