MAPKs represent novel therapeutic targets for gastrointestinal motility disorders

Figure 1 Conventional mechanisms of smooth muscle contraction. Smooth muscle contraction is primarily governed by the phosphorylation of the regulatory light chain (LC₂₀) of myosin II which is in turn driven by the balance between protein kinases responsible for phosphorylation of LC₂₀ and protein phosphatases responsible for its dephosphorylation. Ca²⁺ sensitization of contractile force can result from the direct phosphorylation of LC₂₀ by Ca²⁺-independent protein kinases and/or inhibition of myosin phosphatase activity by Ca²⁺-independent protein kinases. CPI-17: protein kinase C-potentiated inhibitory protein for protein phosphatase 1 of 17 kDa; ILK: integrin-linked kinase; LC₂₀: 20 kDa myosin light chain; MLCK: myosin light chain kinase; MYPT1: myosin targeting subunit 1 of myosin light chain phosphatase; M20: a 20 kDa non-catalytic subunit of myosin light chain phosphatase; PKC: protein kinase C; PP-1: catalytic subunit of protein phosphatase type-1; ROK: Rho-activated protein kinase; ZIPK: zipper-interacting protein kinase.