Myosin phosphatase: subunits and interactions

Abstract

Myosin phosphorylation is an important mechanism in regulating contractile activity of smooth muscle. The level of myosin phosphorylation depends on the balance of two enzymes, myosin light chain kinase and myosin phosphatase. Recently it has been discovered that myosin phosphatase can be regulated and this renewed interest in characterization of the phosphatase. It is suggested that the myosin phosphatase is composed of three subunits: a catalytic subunit of type 1 phosphatase (delta isoform; PP1c delta); and two non-catalytic subunits, large and small (M20). The large subunit is thought to be a targeting subunit and is termed myosin phosphatase target subunit (MYPT). There are several isoforms of MYPT and two genes have been identified on human chromosomes 1 and 12. A dominant feature of MYPT is a series of ankyrin repeats at the N-terminal end of the molecule and these may be involved in binding to the catalytic subunit and to substrate, phosphorylated myosin. In addition, at the N-terminal fringe of the ankyrin motifs is a consensus PP1c binding motif. The function of the M20 subunit is not established but is known to bind to the C-terminal end of MYPT. Various interactions between subunits that might be relevant for the regulation of phosphatase activity are discussed.

Fibronectin's Central Cell-binding Domain Supports Focal Adhesion Formation and Rho Signal Transduction

“…ROCK also inhibits myosin phosphatase by phosphorylation of its myosin-binding subunit (MBS; also named MYPT1) at Thr-853 and Thr-695 (numbers based on human sequence) (42)(43)(44)(45). Therefore, ROCK promotes MLC phosphorylation by direct phosphorylation and by inactivation of myosin phosphatase (46,47). We have recently found that ppMLC T18/S19 , pMLC S19 , and phosphorylation of MBS at Thr-853 (pMBS T853 ) are dependent on Rho and ROCK in human fibroblasts.…”

Differential Association and Localization of Myosin Phosphatase Subunits During Agonist-Induced Signal Transduction in Smooth Muscle

“…21 One possibility, suggested by Gong et al, 28 is that the gizzard MP was dissociated by arachidonic acid release. As pointed out previously, 29 an attractive feature of this idea is the precedent involving dissociation and regulation of glycogen-associated phosphatase after phosphorylation by PKA. 30 It is not known if PGF2␣ induces an increase in arachidonic acid, but the results of Gong et al 28 offer an interesting option for dissociation of MP in ferret portal vein cells.…”

“…One such mechanism is via phosphorylation of MYPT1 at an inhibitory site, ie, T695 in the larger chicken gizzard isoform. 29 This originated with the observation of Trinkle-Mulcahy et al 31 that incubation of permeabilized rabbit portal vein strips with ATP␥S caused thiophosphorylation of MYPT1 and inhibition of MP activity. Subsequently, it was found that a kinase(s) that co-purified with the MP preparations also phosphorylated MYPT1 at T695 and inhibited phosphatase activity.…”

Is myosin phosphatase regulated in vivo by inhibitor‐1? Evidence from inhibitor‐1 knockout mice

“…With respect to the portal vein, the rightward shift in the isoproterenolinduced relaxation in I-1 (_/_) tissues suggests that I-1 may serve as a fine-tuning mechanism in regulating contractility in response to b-adrenergic agonists. The difference between the PKA effects of I-1 protein ablation in aorta and portal vein may reflect inherent differences in the myosin-targeting subunits or catalytic subunits themselves in each tissue (Hartshorne, 1998;Hartshorne et al 1998). In the light of the significant amount of I-1 present, other functions for I-1 in vascular smooth muscle are a strong possibility, but remain elusive.…”