Characterization and function of MYPT2, a target subunit of myosin phosphatase in heart

Okamoto, Ryuji; Kato, Takaaki; Mizoguchi, Akira; Takahashi, Nobuaki; Nakakuki, Tetsuya; Mizutani, Hideo; Isaka, Naoki; Imanaka‐Yoshida, Kyoko; Kaibuchi, Kozo; Lu, Zhaojiang; Mabuchi, Katsuhide; Tao, Terenc; Hartshorne, David J.; Nakano, Takeshi; M, Ito

doi:10.1016/j.cellsig.2005.11.001

Cited by 55 publications

(60 citation statements)

References 39 publications

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“…An interesting recent development is the discovery that there are five proteins that may act as the MBS (MYPT1, MYPT2, MYPT3, MBS85 and TIMAP) [56]. The best characterized MBS is the ubiquitously-expressed MYPT1 protein, it appears that the more tissue-restricted MYPT2 likely functions and is regulated similarly [56]. The other MBS proteins have not been studied extensively and their roles in regulating MLC phosphorylation remains to be determined.…”

Section: Acto-myosin Contractionmentioning

confidence: 99%

“…The MBS is a critical component of the complex as it brings together the phosphatase catalytic subunit with its cognate substrate and because of the role it plays in regulating phosphatase activity. An interesting recent development is the discovery that there are five proteins that may act as the MBS (MYPT1, MYPT2, MYPT3, MBS85 and TIMAP) [56]. The best characterized MBS is the ubiquitously-expressed MYPT1 protein, it appears that the more tissue-restricted MYPT2 likely functions and is regulated similarly [56].…”

Section: Acto-myosin Contractionmentioning

confidence: 99%

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The actin cytoskeleton in cancer cell motility

Olson

Sahai

2008

Clin Exp Metastasis

493

392

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Cancer cell metastasis is a multi-stage process involving invasion into surrounding tissue, intravasation, transit in the blood or lymph, extravasation, and growth at a new site. Many of these steps require cell motility, which is driven by cycles of actin polymerization, cell adhesion and acto-myosin contraction. These processes have been studied in cancer cells in vitro for many years, often with seemingly contradictory results. The challenge now is to understand how the multitude of in vitro observations relates to the movement of cancer cells in living tumour tissue. In this review we will concentrate on actin protrusion and acto-myosin contraction. We will begin by presenting some general principles summarizing the widely-accepted mechanisms for the co-ordinated regulation of actin polymerization and contraction. We will then discuss more recent studies that investigate how experimental manipulation of actin dynamics affects cancer cell invasion in complex environments and in vivo.

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Section: Acto-myosin Contractionmentioning

confidence: 99%

Section: Acto-myosin Contractionmentioning

confidence: 99%

The actin cytoskeleton in cancer cell motility

Olson

Sahai

2008

Clin Exp Metastasis

493

392

View full text Add to dashboard Cite

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“…Western blots were performed as described previously 7 with antibodies directed against MYPT1, 13 MYPT2, 14 PP1cα (Cell Signaling), PP1cδ , PP1cγ (a gift from Dr Shima), 15 leucine zipper motif of MYPT1 (found also at the C-termini of MYPT2 and HS-M21, a heart specific isoform of smooth muscle M20 16 ), phospholamban (PLB; Affinity BioReagents), phospho-PLB (Ser16; Upstate), troponin I (TnI; Cell Signaling), cardiac phospho-TnI (Ser23/24; Cell Signaling), slow skeletal TnI (Santa Cruz), smooth muscle MLCK, 17 and skeletal muscle MLCK (Santa Cruz). Total protein concentration was measured using the Bradford assay (Bio-Rad) and equal amounts of protein were loaded into each well.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Our recent in-vitro study showed that MYPT2 could form a complex with type 1 phosphatase catalytic subunit δ isoform (PP1cδ) that served as an MP holoenzyme in cardiac muscle cells. 7 However, whether MYPT2 together with PP1cδ plays a principle role in the dephosphorylation of cardiac MLC in the living heart has remained to be investigated.…”

mentioning

confidence: 99%

Overexpression of Myosin Phosphatase Reduces Ca2+ Sensitivity of Contraction and Impairs Cardiac Function

Mizutani

Okamoto

Moriki

et al. 2010

Circ J

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Background: Phosphorylation of the regulatory light chain of myosin (MLC) has roles in cardiac function. In vitro, myosin phosphatase target subunit 2 (MYPT2) is a strongly suspected regulatory subunit of cardiac myosin phosphatase (MP), but there is no in-vivo evidence regarding the functions of MYPT2 in the heart. Methods and Results:Transgenic mice (Tg) overexpressing MYPT2 were generated using the α-MHC promoter. Tg hearts showed an increased expression of MYPT2 and concomitant increase of the endogenous catalytic subunit of type 1 phosphatase (PP1cδ), resulting in an increase of the MP holoenzyme. The level of phosphorylation of ventricular MLC was reduced. The pCa-tension relationship, using β-escin permeabilized fibers, revealed decreased Ca 2+ sensitization of contraction in the Tg heart. LV enlargement with associated impairment of function was observed in the Tg heart and ultrastructural examination showed cardiomyocyte degeneration. Conclusions:Overexpression of MYPT2 and the increase in PP1cδ resulted in an increase of the MP holoenzyme and a decrease in the level of MLC phosphorylation. The latter induced Ca 2+ desensitization of contraction and decreased LV contractility, resulting in LV enlargement. Thus, MYPT2 is truly the regulatory subunit of cardiac MP in-vivo and plays a significant role in modulating cardiac function. (Circ J 2010; 74: 120 - 128)

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“…In cardiomyocytes, overexpression of myosin phosphatase subunits results in the abolition of agonist-induced sarcomere organization, a marker of cardiac hypertrophy (Okamoto et al 2006). Interestingly, an HDAC5 mutant that cannot be phosphorylated (similar to our HDAC7⌬P) is refractory to hypertrophic signaling and inhibits cardiomyocyte hypertrophy (Zhang et al 2002).…”

Section: Resultsmentioning

confidence: 99%

Myosin phosphatase dephosphorylates HDAC7, controls its nucleocytoplasmic shuttling, and inhibits apoptosis in thymocytes

Parra¹,

Mahmoudi²,

Verdin³

2007

Genes Dev.

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+ double-positive thymocytes, is regulated by its nucleocytoplasmic shuttling. In resting thymocytes, HDAC7 is nuclear and functions as a transcriptional repressor. After T-cell receptor (TCR) activation, the serine/threonine kinase PKD1 phosphorylates HDAC7, resulting in its nuclear export and the derepression of its target genes. Here, we identify protein phosphatase 1␤ (PP1␤) and myosin phosphatase targeting subunit 1 (MYPT1), two components of the myosin phosphatase complex, as HDAC7-associated proteins in thymocytes. Myosin phosphatase dephosphorylates HDAC7 and promotes its nuclear localization, leading to the repression of the HDAC7 target, Nur77, and the inhibition of apoptosis in CD4 + CD8 + thymocytes.Supplemental material is available at http://www.genesdev.org.

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Characterization and function of MYPT2, a target subunit of myosin phosphatase in heart

Cited by 55 publications

References 39 publications

The actin cytoskeleton in cancer cell motility

The actin cytoskeleton in cancer cell motility

Overexpression of Myosin Phosphatase Reduces Ca2+ Sensitivity of Contraction and Impairs Cardiac Function

Myosin phosphatase dephosphorylates HDAC7, controls its nucleocytoplasmic shuttling, and inhibits apoptosis in thymocytes

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