Diffusion of myosin light chain kinase on actin: A mechanism to enhance myosin phosphorylation rates in smooth muscle

Smooth muscle myosin (SMM) light chain kinase (MLCK; UniProt accession no. Q15746-7) is a Ca-calmodulin (CaM)–activated kinase (Hong et al., 2011) that is required for smooth muscle contraction (Itoh et al., 1989; He et al., 2008; Zhang et al., 2010) and regulation of tone in most of the hollow organs of the body (Kamm and Stull, 2011). It phosphorylates the regulatory light chains (RLCs) of SMM (a myosin II), causing a switch from low to high actin–activated myosin ATPase activity. Similar kinases modulate the activities of other myosin IIs in skeletal and cardiac muscles, and also in nonmuscle cells (Kamm and Stull, 2001). The predominant form of MLCK in smooth muscle (Fig. 1 A) is a long multi-domain protein (Mabuchi et al., 2010) containing an N-terminal actin-binding domain (ABD; three DFRXXL motifs; Gallagher and Stull, 1997) within the first 75 residues, IgG and Fn domains, a kinase domain, and a C-terminal myosin-binding domain