Figure 1.

Intracellular signalling underlying vascular smooth muscle cells contraction. Contraction is induced by the increased phosphorylation of 20 kDa myosin light chain (MLC). Activation of G protein-coupled receptors (GPCR) triggers both Ca²⁺-dependent phosphorylation of MLC and calcium facilitation inhibiting MLC dephosphorylation. G_q-11 protein activates phospholipase C (PLC) and induces intracellular Ca²⁺ rise through inositol (1,4,5) triphosphate (Ins(1,4,5)P₃)-sensitive endoplasmic reticulum stores. This adds to extracellular Ca²⁺ entry through voltage-gated calcium channels (VGCCs) and transient receptor potential (TRP) channels. The Ca²⁺-Calmodulin complex (Ca²⁺-CAM) induces the phosphorylation of MLCK. The second product of PLC, diacylglycerol (DAG), activates protein kinase C (PKC), which, through its substrate CPI-17, inhibits MLCP, and thus, MLC dephosphorylation. G_12-13 activates Rho guanine nucleotides exchanging factor (Rho-GEF) that activates RhoA protein through GDP exchange to GTP. GTP-bound Rho activates Rho-kinase which, through MLCP phosphorylation, inhibits MLC dephosphorylation.