Role of protein phosphatase type 1 in contractile functions: myosin phosphatase.

Protein phosphatase type 1 (PP1) is involved in a wide range of cell activities (1), and even within the more restricted theme of contractile activity in muscle several processes may be considered. Important areas include regulation of ion channels (2), effect of phospholamban on Ca uptake by the SR (3), and phosphorylation-dephosphorylation of myosin II. Phosphorylation of myosin light chains (located in the head-neck junction of the myosin molecule) by the Ca -calmodulin-dependent MLCK in all muscle types is established (4). Discovery of MLCK spurred numerous reports on the phosphatases involved. In smooth muscle, phosphorylation of myosin II increases actin-activated ATPase activity and is required for contraction (4). Much of the earlier work focused on smooth muscle myosin phosphatase (MP). An initial controversy was the type of catalytic subunit involved, i.e. PP1c, PP2Ac, etc. In smooth muscle the majority of MP activity is due to PP1c (5), and this finding was extended to include skeletal and cardiac muscle. Three genes encode PP1c: , , and (also called ). Five PP1c isoforms are expressed, where 1/ 2 and 1/ 2 are generated by alternative splicing (1). To accommodate specific functions of the limited number of PP1c isoforms with the multiple roles of PP1c the concept of target subunits was developed. Over 50 potential target subunits have been identified (1) that in complex with PP1c may designate specific substrates, regulate activity, and direct distinct cell localization. This review describes one of the PP1 holoenzymes, namely the myosin phosphatase of muscle.