Schematic representation of the AT1R-modulated gene regulatory network model. Ang II binding to AT1R leads to activation of signaling kinases (ERK, FRK, and JNK), which regulate the AP-1 family of transcription factors through fast (protein phosphorylation) and slow (protein synthesis) cellular processes. Activated signaling kinases phosphorylate downstream transcription factors (Elk-1, c-Fos, c-Jun, ATF-2) leading to their subsequent DNA-binding activity. Active AP-1 family of transcription factors considered here are the heterodimers of dual phosphorylated c-Fos and c-Jun or homodimers of dual phosphorylated c-Jun. These AP-1 forms induce transcription of Tyrosine hydroxylase (TH), a critical regulator of neuronal function. Reactions leading to activation of ppc-Fos:ppc-Jun are highlighted in light grey, and reactions leading to activation of ppc-Jun:ppc-Jun in dark grey.
Miller et al. BMC Systems Biology 2010 4:171 doi:10.1186/1752-0509-4-171