Mechanisms of PPAR-ERK signaling crosstalk:
(a) serine phosphorylation of PPAR
by the ERK cascade suppresses the
classical genomic action of RXR/PPAR heterodimers on PPREs in the DNA; (b) ERK cascade phosphorylation
of promitotic and proinflammatory transcription factors (TF) and NR coactivators (NCoA) modulates
their interaction with PPAR “On-DNA”; (c) nuclear export of PPAR by MEK1 may result in “Off-DNA”
interactions of PPAR with alternative protein partners in the cytoplasm; (d) PPAR-independent
ERK cascade activation by PPAR ligands through plasma membrane GPCRs, transactivation of the EGFR
(black bars), or calcium signaling.
