Myosin phosphatase: Structure, regulation and function

Masaaki Ito, Takeshi Nakano, F. Erdődi, David J. Hartshorne

Research output: Contribution to journalArticle

335 Citations (Scopus)

Abstract

Phosphorylation of myosin II plays an important role in many cell functions, including smooth muscle contraction. The level of myosin II phosphorylation is determined by activities of myosin light chain kinase and myosin phosphatase (MP). MP is composed of 3 subunits: a catalytic subunit of type 1 phosphatase, PP1c; a targeting subunit, termed myosin phosphatase target subunit, MYPT; and a smaller subunit, M20, of unknown function. Most of the properties of MP are due to MYPT and include binding of PP1c and substrate. Other interactions are discussed. A recent discovery is the existence of an MYPT family and members include, MYPT1, MYPT2, MBS85, MYPT3 and TIMAP. Characteristics of each are outlined. An important discovery was that the activity of MP could be regulated and both activation and inhibition were reported. Activation occurs in response to elevated cyclic nucleotide levels and various mechanisms are presented. Inhibition of MP is a major component of Ca2+-sensitization in smooth muscle and various molecular mechanisms are discussed. Two mechanisms are cited frequently: (1) Phosphorylation of an inhibitory site on MYPT1, Thr696 (human isoform) and resulting inhibition of PP1c activity. Several kinases can phosphorylate Thr696, including Rho-kinase that serves an important role in smooth muscle function; and (2) Inhibition of MP by the protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17). Examples where these mechanisms are implicated in smooth muscle function are presented. The critical role of RhoA/Rho-kinase signaling in various systems is discussed, in particular those vascular smooth muscle disorders involving hypercontractility.

Original languageEnglish
Pages (from-to)197-209
Number of pages13
JournalMolecular and Cellular Biochemistry
Volume259
Issue number1-2
DOIs
Publication statusPublished - Apr 2004

Fingerprint

Myosin-Light-Chain Phosphatase
Muscle
Phosphorylation
Smooth Muscle
Myosin Type II
rho-Associated Kinases
Chemical activation
Myosin-Light-Chain Kinase
Cyclic Nucleotides
Phosphoric Monoester Hydrolases
Muscular Diseases
Protein Kinase C
Muscle Contraction
Vascular Smooth Muscle
Protein Isoforms
Phosphotransferases
Catalytic Domain
Substrates

Keywords

  • Ca sensitization
  • CPI-17
  • Myosin phosphate
  • MYPT1
  • Rho
  • Rho-kinase
  • Smooth muscle
  • Type 1 phosphatase

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Myosin phosphatase : Structure, regulation and function. / Ito, Masaaki; Nakano, Takeshi; Erdődi, F.; Hartshorne, David J.

In: Molecular and Cellular Biochemistry, Vol. 259, No. 1-2, 04.2004, p. 197-209.

Research output: Contribution to journalArticle

Ito, Masaaki ; Nakano, Takeshi ; Erdődi, F. ; Hartshorne, David J. / Myosin phosphatase : Structure, regulation and function. In: Molecular and Cellular Biochemistry. 2004 ; Vol. 259, No. 1-2. pp. 197-209.
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