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(Circulation Research. 2002;90:500.)
© 2002 American Heart Association, Inc.

Editorials

Myosin Light Chain Phosphatase

It Gets Around

Frank V. Brozovich

From the Departments of Medicine (Cardiology) and Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio.

Correspondence to Frank V. Brozovich, Division of Cardiology, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106-5038. E-mail fxb9@po.cwru.edu

Key Words: agonist • smooth muscle • myosin targeting subunit • Rho A • G protein

The importance of Ca²⁺calmodulin-dependent myosin light chain kinase (MLCK) for smooth muscle contraction is well documented.¹ Until recently, myosin light chain (MLC) phosphatase was thought to be unregulated and constitutively active. However, studies have demonstrated that smooth muscle contraction is dependent on regulation of MLC phosphatase activity.^2,3 The inhibition of phosphatase activity increases force at a constant [Ca²⁺], whereas a stimulation of MLC phosphatase activity reduces force at a constant [Ca²⁺].

MLC Phosphatase

MLC phosphatase isolated from smooth muscle is a holoenzyme consisting of 3 subunits²: a small 20-kDa subunit, an 38-kDa catalytic subunit, and a myosin-targeting subunit (MYPT) of 110 to 133 kDa. The small subunit has no established function and is not required for either catalytic activity or activation of PP1c.² The catalytic subunit is a PP1c phosphatase, and the isoform is associated with the holoenzyme.⁴ The large subunit is the MYPT. Isoform diversity of MYPT was first shown in chicken where 2 isoforms (M130 and M133)² were shown to differ by the presence of a central insert between aa residues 512 to 552.⁵ Similar isoform diversity has been demonstrated for MYPT isolated from other species.^2,6 In addition to the isoform diversity produced by the central insert, alternative splicing of a COOH-terminal exon leads to MYPT isoforms, which differ by the presence or absence of a leucine zipper.⁷

Agonist-Induced Force Enhancement

At any intracellular [Ca⁺²], force for an agonist stimulated contraction is higher than for depolarization.^8,9 This phenomenon has been termed agonist-induced force enhancement, or Ca⁺² sensitization, and . . . [Full Text of this Article]

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