Mice develop normally in the absence of Smad4 nucleocytoplasmic shuttling.

ABSTRACT: Smad4 in partnership with R-Smads (receptor-regulated Smads) activates TGF-beta (transforming growth factor-beta)-dependent signalling pathways essential for early mouse development. Smad4 null embryos die shortly after implantation due to severe defects in cell proliferation and visceral endoderm differentiation. In the basal state, Smad4 undergoes continuous shuttling between the cytoplasm and the nucleus due to the combined activities of an N-terminal NLS (nuclear localization signal) and an NES (nuclear export signal) located in its linker region. Cell culture experiments suggest that Smad4 nucleocytoplasmic shuttling plays an important role in TGF-beta signalling. In the present study we have investigated the role of Smad4 shuttling in vivo using gene targeting to engineer two indepen

SUBMITTER: Biondi CA 

PROVIDER: S-EPMC1868808 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature