Smooth muscle signalling pathways in health and disease

Introduction Mechanisms that regulate LC20 phosphorylation Regulation of myosin phosphatase CaMKII Mechanisms that regulate the access of myosin to actin Caldesmon bCaP function in regulation of PKC and ERK signalling Mechanisms that regulate cytoskeletal remodelling Conclusions Smooth muscle contractile activity is a major regulator of function of the vascular system, respiratory system, gastrointestinal system and the genitourinary systems. Malfunction of contractility in these systems leads to a host of clinical disorders, and yet, we still have major gaps in our understanding of the molecular mechanisms by which contractility of the differentiated smooth muscle cell is regulated. This review will summarize recent advances in the molecular understanding of the regulation of smooth muscle myosin activity via phosphorylation/dephosphorylation of myosin, the regulation of the accessibility of actin to myosin via the actin-binding proteins calponin and caldesmon, and the remodelling of the actin cytoskeleton. Understanding of the molecular 'players' should identify target molecules that could point the way to novel drug discovery programs for the treatment of smooth muscle disorders such as cardiovascular disease, asthma, functional bowel disease and pre-term labour.