The Grb2/Mek pathway represses Nanog in murine embryonic stem cells.

摘要: The homeobox gene Nanog is a key intrinsic determinant of self renewal in embryonic stem (ES) cells, and its repression leads ES cells to selectively differentiate into primitive endoderm. Although occurs at the outermost layer cell aggregates independent leukemia inhibitory factor (LIF)/STAT3 pathway, it largely undetermined what external cues intracellular signals cause event. Of interest, addition tyrosine phosphatase inhibitor, sodium vanadate, repressed transcription without any detectable changes upstream transcriptional regulators Oct3/4 Sox2. Furthermore, vanadate induced endoderm differentiation, even inner aggregates. Expression Gata6 Zfp42, two putative downstream effectors, was also increased decreased by respectively, but these were eliminated exogenous expression. effects abrogated Grb2 deficiency or Mek PD98059. Indeed, PD98059 prevented aggregation as well. transfection constitutive active mutant differentiation. These data indicate that Grb2/Mek pathway primarily mediates upon differentiation