Phosphorylation of the myofibrillar proteins and the regulation of contractile activity in muscle.

Abstract

Evidence now exists for the phosphorylation of all the major proteins of the myofibril with the exception of troponin C. Although uncertainty exists in most cases about the role of phosphorylation of the myofibrillar proteins, there is substantial evidence that phosphorylation of serine 20 of rabbit cardiac troponin I leads to a lowering of the sensitivity of the actomyosin ATPase to Ca2+. This process is of special importance in the physiological response of the heart to adrenalin. A well defined enzymic system involving a specific kinase and a phosphatase is present in most muscles for the phosphorylation and dephosphorylation of the P light chain (regulatory, L2 or DTNB light chain) of myosin. Myosin light-chain kinase is very active in fast skeletal muscles, and although it is unlikely that phosphorylation followed by dephosphorylation of the P light chain occurs fast enough to be synchronous with the contractile cycle, phosphorylation may have a modulatory role in this tissue. Both post-tetanic potentiation and the reduced actomyosin ATPase turnover rate observed in fast-twitch muscle as a consequence of sustained forceful contraction have been suggested by different investigators to be consequences of P light chain phosphorylation. Nevertheless, unequivocal evidence associating either of these effects with phosphorylation is not yet available. Kinase activity is also high in vertebrate smooth muscle and it has been suggested that phosphorylation of the P light chain is the process that activates the actomyosin ATPase in this tissue. Evidence from a number of studies indicates, however, that regulation of smooth muscle actomyosin ATPase may not be a simple phosphorylation-dephosphorylation process.