Role of Fas-associated death domain-containing protein (FADD) phosphorylation in regulating glucose homeostasis: from proteomic discovery to physiological validation.

ABSTRACT: Fas-associated death domain-containing protein (FADD), a classical apoptotic signaling adaptor, participates in different nonapoptotic processes regulated by its phosphorylation. However, the influence of FADD on metabolism, especially glucose homeostasis, has not been evaluated to date. Here, using both two-dimensional electrophoresis and liquid chromatography linked to tandem mass spectrometry (LC/MS/MS), we found that glycogen synthesis, glycolysis, and gluconeogenesis were dysregulated because of FADD phosphorylation, both in MEFs and liver tissue of the mice bearing phosphorylation-mimicking mutation form of FADD (FADD-D). Further physiological studies showed that FADD-D mice exhibited lower blood glucose, enhanced glucose tolerance, and increased liver glycogen content without altera

SUBMITTER: Yao C 

PROVIDER: S-EPMC3790283 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature