@entity19 F9 embryocarcinoma (EC) cells constitute a well established cell-autonomous model system for investigating @entity554 signaling in vitro as, depending on culture conditions, @entity1968 (RA) can induce their differentiation into either primitive, parietal or visceral extraembryonic endoderm-like cells. These RA-induced differentiations are accompanied by decreases in proliferation rates, modifications of expression of subsets of RA-target genes, and induction of apoptosis. To elucidate the roles played by the multiple @entity554 receptors (RARs and RXRs) in response to RA treatments, F9 EC cells lacking one or several RARs or RXRs were engineered through homologous recombination. Mutated RARs and/or RXRs were then reexpressed in given RAR or RXR null backgrounds. WT and mutant cells were also treated with different combinations of ligands selective for RXRs and/or for each of the three RAR isotypes. These studies lead to the conclusion that most RA-induced events (e.g. primitive and visceral differentiation, @entity851 , apoptosis and activation of expression of a number of genes) are transduced by @entity19915 / @entity19914 heterodimers, whereas some other events (e.g. parietal differentiation) are mediated by @entity14933 / @entity19914 . heterodimers. They also demonstrate that both @entity69959 and AF-2 activation functions of RARs and RXRs, as well as their phosphorylation, are differentially required in these RA-induced events. In @entity19915 / @entity19914 heterodimers, the phosphorylation of @entity19915 is necessary for triggering primitive differentiation, while that of @entity19914 is required for @entity851 . On the other hand, phosphorylation of @entity14933 is necessary for parietal differentiation. Thus, @entity554 receptors are sophisticated signal integrators that transduce not only the effects of their cognate ligands, but also those of ligands that bind to membrane receptors.

F9 embryocarcinoma cells: a cell autonomous model to study the functional selectivity of RARs and RXRs in XXXX signaling.

@entity851 :: ('MESH:D006130', 'Disease') :: ['growth arrest'] @entity19 :: ('10090', 'Species') :: ['Mouse'] @entity14933 :: ('19401(Tax:10090)', 'Gene') :: ['RARalpha'] @entity19915 :: ('19411(Tax:10090)', 'Gene') :: ['RARgamma'] @entity69959 :: ('19185(Tax:10090)', 'Gene') :: ['AF-1'] @entity19914 :: ('20181(Tax:10090)', 'Gene') :: ['RXRalpha'] @entity1968 :: ('MESH:D014212', 'Chemical') :: ['retinoic acid'] @entity554 :: ('CHEBI:26537', 'Chemical') :: ['retinoid']
@entity554 :: (CHEBI:26537,Chemical) :: ['retinoid']
