Figure 8. Ribosomal S6 kinase (RSK) signaling scheme for regulation of Ca²⁺-independendent contraction of smooth muscle.

Agonists through GPCRs leads to activation of sequential ERK1/2 phosphorylations of RSK, subsequent RSK autophosphorylation by its C-terminal kinase domain (CTKD), the recruitment of phosphoinositide-dependent kinase 1 (PDK1) to this newly phosphorylated site, and finally PDK1-dependent phosphorylation at Ser227, with concomitant activation of the NTKD. Active RSK increases RLC₂₀ phosphorylation, either directly or indirectly, as well as inhibitory phosphorylation of MYPT1 at Thr696/853 augmenting Rho/ROCK phosphorylation of these sites. Potential RSK phosphorylation of Ser668 on MYPT1 is also indicated.