Protein kinase C in the regulation of smooth muscle contraction.
The cellular and molecular mechanisms underlying smooth muscle contraction are reviewed in the light of recent studies of smooth muscle ultrastructure and of the role of polyphosphoinositide turnover and protein kinase C function in smooth muscle contraction. A new model of smooth muscle contraction is proposed that differs radically from accepted views, particularly the latch bridge hypothesis, in terms of both Ca2+ messenger function and the molecular events underlying this process. A coordinate fibrillar domain model of contraction is proposed in which the initial and sustained phases of contraction are mediated by different cellular and molecular events. The initial phase of response is mediated by a rise in [Ca2+]c and the resulting calmodulin-dependent activation of both myosin light chain kinase and the dissociation of caldesmon from the actin-caldesmon-tropomyosin-myosin fibrillar domain. These events lead to an interaction between actin and the phosphorylated light chains of myosin just as in previous models. However, this initial phase is followed by a sustained phase in which a rise in [Ca2+]sm stimulates the plasma membrane-associated, Ca2+-sensitive form of protein kinase C that results in the phosphorylation of both structural and regulatory components of the filamin-actin-desmin fibrillar domain. These events underlie the tonic phase of contraction.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D008954:Models, Biological; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D009219:Myosin-Light-Chain Kinase / Q000502:physiology; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*
D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D000251:Adenosine Triphosphatases; D002118:Calcium