FIG. 8.

Some aspects of the RAR/RXR and MAPK relationships in mesodermal differentiation of P19 cells. Lines ending with an arrowhead indicate stimulatory effects, and lines ending with a small perpendicular bar indicate inhibitory effects. Activation of RAR and RXR by atRA concurrently induces adipogenesis and myogenesis. Treatments favoring RAR over RXR signaling preferentially induce adipogenesis over myogenesis (TTNPB and atRA + RXRatg treatments). Treatments favoring RXR over RAR signaling permit both differentiation routes (LG268 and atRA + RARatg treatments). Inhibitors of p38 (p38i) and ERK (ERKi) signaling have differential effects on mesodermal differentiation depending upon the cellular retinoid status. P38i enhances myogenesis and adipogenesis when RAR and RXR are activated, inhibits both differentiation routes under the predominance of RXR signaling, and increases the antimyogenic action of RAR when RAR signaling predominates. ERKi increases myogenesis when RAR and RXR are activated, but has no influence on myogenesis or on adipogenesis when either RAR or RXR signaling predominates.