These data indicate that the Grb2/Mek pathway primarily mediates Nanog gene repression upon ES cell differentiation into primitive endoderm. 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.

Grb2 deficiency abrogated the effects of sodium vanadate on Nanog repression. Grb2 has an SH2 domain that specifically binds to a peptide motif containing a phosphotyrosine. Thus, it works as an adaptor protein, linking the signals received by receptor tyrosine kinases, such as FGF receptors, to their downstream targets.

Signaling molecules involved in NANOG repression by primitive endoderm specification include GRB2/SOS/Ras and ERK. The canonical ERK cascade is stimulated upon the binding of extracellular growth factors to their respective transmembrane RTKs.

2011年12月13日 · The pan-ICM Gata6 expression in Nanog mutants together with the pan-ICM Nanog expression in Grb2 mutants (Chazaud et al., 2006) supports the model of reciprocal inhibition of Nanog and RTK pathways to induce either epiblast or PrE differentiation.

2006年5月1日 · In embryos lacking Grb2 where no PE forms, Gata6 expression was lost and all ICM cells were Nanog positive. We propose a model in which the ICM develops as a mosaic of EPI and PE progenitors at E3.5, dependent on Grb2-Ras-MAP kinase signaling, followed by later segregation of the progenitors into the appropriate cell layers.

2015年9月25日 · Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs). Insight into the regulation of Nanog is important for a better understanding of the molecular mechanisms that control pluripotency of mESCs. In a silico analysis, we identify four GATA-1 putative binding sites in Nanog proximal promoter.

2006年11月1日 · These data indicate that the Grb2/Mek pathway primarily mediates Nanog gene repression upon ES cell dif ferentiation into primitive endoderm. The homeoprotein Nanog was found to play an...

2022年9月6日 · Here, we show that a dose‐dependent induction of Fgfbp1 and Fgfr2 by NANOG activates autocrine‐mediated ERK signaling in Nanog ‐high cells to trigger autorepression. pERK recruits NONO to the Nanog locus to repress transcription by preventing POL2 loading.

2013年7月18日 · Interestingly, miR-200a directly targets growth factor receptor-bound protein 2 (Grb2), which is a key adaptor in the Erk signaling pathway. Furthermore, high levels of miR-200a dramatically decrease Grb2 levels and suppress the appearance of mesoderm and endoderm lineages in embryoid body formation, as well as suppressing the activation of Erk.

Nanog directly represses GATA6, which results in repression of GATA4, thereby inhibiting ESC differentiation. Nanog also regulates the expression of Oct4 and SOX2 genes, which play important roles in pluripotency. Nanog also activates functions in concert with other factors, such as Oct4 and SOX2, to establish ESC identity.