関: myosin phosphatase

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very thin and insubstantial; "thin paper"; "light summer dresses"
make lighter or brighter; "This lamp lightens the room a bit" (同)illume, illumine, light_up, illuminate
a condition of spiritual awareness; divine illumination; "follow Gods light" (同)illumination
having abundant light or illumination; "they played as long as it was light"; "as long as the lighting was good" (同)lighting
(physics) electromagnetic radiation that can produce a visual sensation; "the light was filtered through a soft glass window" (同)visible_light, visible_radiation
any device serving as a source of illumination; "he stopped the car and turned off the lights" (同)light_source
the visual effect of illumination on objects or scenes as created in pictures; "he could paint the lightest light and the darkest dark" (同)lightness
a particular perspective or aspect of a situation; "although he saw it in a different light, he still did not understand"
a person regarded very fondly; "the light of my life"
a visual warning signal; "they saw the light of the beacon"; "there was a light at every corner"
an illuminated area; "he stepped into the light"
mental understanding as an enlightening experience; "he finally saw the light"; "can you shed light on this problem?"
public awareness; "it brought the scandal to light"
(used of color) having a relatively small amount of coloring agent; "light blue"; "light colors such as pastels"; "a light-colored powder" (同)light-colored
moving easily and quickly; nimble; "the dancer was light and graceful"; "a lightsome buoyant step"; "walked with a light tripping step" (同)lightsome, tripping
having relatively few calories; "diet cola"; "light (or lite) beer"; "lite (or light) mayonnaise"; "a low-cal diet" (同)lite, low-cal, calorie-free
less than the correct or legal or full amount often deliberately so; "a light pound"; "a scant cup of sugar"; "regularly gives short weight" (同)scant, short
(of sleep) easily disturbed; "in a light doze"; "a light sleeper"; "a restless wakeful night" (同)wakeful
(physics, chemistry) not having atomic weight greater than average; "light water is ordinary water"
(used of soil) loose and large-grained in consistency; "light soil"
characterized by or emitting light; "a room that is light when the shutters are open"; "the inside of the house was airy and light"
demanding little effort; not burdensome; "light housework"; "light exercise"
designed for ease of movement or to carry little weight; "light aircraft"; "a light truck"
easily assimilated in the alimentary canal; not rich or heavily seasoned; "a light diet"
having little importance; "losing his job was no light matter"
intended primarily as entertainment; not serious or profound; "light verse"; "a light comedy"
not great in degree or quantity or number; "a light sentence"; "a light accent"; "casualties were light"; "light snow was falling"; "light misty rain"; "light smoke from the chimney"
of comparatively little physical weight or density; "a light load"; "magnesium is a light metal--having a specific gravity of 1.74 at 20 degrees C"
of little intensity or power or force; "the light touch of her fingers"; "a light breeze"
of the military or industry; using (or being) relatively small or light arms or equipment; "light infantry"; "light cavalry"; "light industry"; "light weapons"
psychologically light; especially free from sadness or troubles; "a light heart"
fasten or secure with chains; "Chain the chairs together"
a unit of length
a necklace made by a stringing objects together; "a string of beads"; "a strand of pearls"; (同)string, strand
a linked or connected series of objects; "a chain of daisies"
a series of (usually metal) rings or links fitted into one another to make a flexible ligament
anything that acts as a restraint
(chemistry) a series of linked atoms (generally in an organic molecule) (同)chemical chain
a series of things depending on each other as if linked together; "the chain of command"; "a complicated concatenation of circumstances" (同)concatenation
(business) a number of similar establishments (stores or restaurants or banks or hotels or theaters) under one ownership
connect or arrange into a chain by linking
apparatus for supplying artificial light effects for the stage or a film
the craft of providing artificial light; "an interior decorator must understand lighting"
any of a group of enzymes that act as a catalyst in the hydrolysis of organic phosphates
British biochemist (born in Germany) who isolated and purified penicillin, which had been discovered in 1928 by Sir Alexander Fleming (1906-1979) (同)Ernst Boris Chain, Sir Ernst Boris Chain

PrepTutorEJDIC

〈U〉『光,光線』;明るさ / 〈U〉夜明け;日中;日光 / 〈C〉『明かり』(太陽・灯火など光を出すもの) / 〈U〉《時にa~》光輝(brightness),(目などの)輝き / 〈C〉(点火するための)火,火花 / 〈C〉明かり採り,採光窓 / 〈C〉《通例単数形で》(絵などの)明るい部分 / 〈U〉(…についての)知識,情報,理解《+『on』+『名』》 / 〈C〉(ものを見る)観点,見地;相 / 〈C〉この世に光を与える人;指導的な人物 / …‘に'『火をつける』《+『up』+『名』+『名』+『up』》 / …‘に'『明かりをつける』,‘を'照らす《+『up』+『名,』+『名』+『up』》 / 〈人〉‘を'明かりをつけて案内する / 〈表情など〉‘を'明るくする《+『up』+『名,』+『名』+『up』》 / 〈物が〉火がつく,点火する;明かりがつく《+『up』》 / 明るくなる,晴れ晴れする《+『up』》 / 『明るい』 / (色が)『薄い』
(重量が)『軽い』 / (いろいろな事について,その程座・量が)軽い,小さい / 『軽快な』 / 軽装の / 肩のこらない;気軽な / 手軽な,骨の折れなし / (食べ物が)消化のよい,もたれない / ふらふらする,目まいのする / アルコール分の少ない / (パンなどが)ふんわりした / (重量が)軽く / (程度が)軽く,容易に;軽装で
(車・馬などから)降りる《+『from』+『名』》(alight) / (木などに)〈鳥などが〉止まる《+『on』(『upon』)+『名』》 / (…に)〈打撃・運などが〉突然ふりかかる《+『on』(『upon』)+『名』》
『鎖』;(装飾用の)鎖 / 《複数形で》『束縛』,拘束;囚人をつなぐ鎖 / (物事の)『連続』,つながり《+『of』+『名』》 / (商店・銀行・ホテルなどの)チェーン(一連の店が同一資本のもとで連携して経営される方式;その店) / チェーン(測量で用いられる単位;約21.7m) / …'を'『鎖でつなぐ』《+『up』(『together』)+『名,』+『名』+『up』(『together』)》
照明,点火 / 照明方法(装置)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/10 19:57:54」(JST)

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Myosin light-chain phosphatase, more commonly called myosin phosphatase (EC 3.1.3.53), is an enzyme (specifically a serine/threonine-specific protein phosphatase) that dephosphorylates the regulatory light chain of myosin II. This dephosphorylation reaction occurs in smooth muscle tissue and initiates the relaxation process of the muscle cells. Thus, myosin phosphatase undoes the muscle contraction process initiated by myosin light-chain kinase. The enzyme is composed of three subunits: the catalytic region (protein phosphatase 1, or PP1), the myosin binding subunit (MYPT1), and a third subunit (M20) of unknown function. The catalytic region uses two manganese ions as catalysts to dephosphorylate the light-chains on myosin, which causes a conformational change in the myosin and relaxes the muscle. The enzyme is highly conserved^[1] and is found in all organisms’ smooth muscle tissue. While it is known that myosin phosphatase is regulated by rho-associated protein kinases, there is current debate about whether other molecules, such as arachidonic acid and cAMP, also regulate the enzyme.^[2]

Function

Smooth muscle tissue is mostly made of actin and myosin,^[3] two proteins that interact together to produce muscle contraction and relaxation. Myosin II, also known as conventional myosin, has two heavy chains that consist of the head and tail domains and four light chains (two per head) that bind to the heavy chains in the “neck” region. When the muscle needs to contract, calcium ions flow into the cytosol from the sarcoplasmic reticulum, where they activate calmodulin, which in turn activates myosin light-chain kinase (MLC kinase). MLC kinase phosphorylates the myosin light chain (MLC₂₀) at the Ser-19 residue. This phosphorylation causes a conformational change in the myosin, activating crossbridge cycling and causing the muscle to contract. Because myosin undergoes a conformational change, the muscle will stay contracted even if calcium and activated MLC kinase concentrations are brought to normal levels. The conformational change must be undone to relax the muscle.^[4]

When myosin phosphatase binds to myosin, it removes the phosphate group. Without the group, the myosin reverts back to its original conformation, in which it cannot interact with the actin and hold the muscle tense, so the muscle relaxes. The muscle will remain in this relaxed position until myosin is phosphorylated by MLC kinase and undergoes a conformational change.

Structure

A 3D representation of PP1 (shown in red) and a portion of MYPT1 (shown in blue), with the manganese ion catalysts shown in white. The yellow lines mark the grooves that are critical for enzyme binding and catalysis.

Myosin phosphatase is made of three subunits. The catalytic subunit, PP1, is one of the more important Ser/Thr phosphatases in eukaryotic cells, as it plays a role in glycogen metabolism, intracellular transport, protein synthesis, and cell division as well as smooth muscle contraction.^[5] Because it is so important to basic cellular functions, and because there are far fewer protein phosphatases than kinases in cells,^[6] PP1’s structure and function is highly conserved (though the specific isoform used in myosin phosphatase is the δ isoform, PP1δ).^[7] PP1 works by using two manganese ions as catalysts for the dephosphorylation (see below).

Surrounding these ions is a Y-shaped cleft with three grooves: a hydrophobic, an acidic, and a C-terminal groove. When PP1 is not bonded to any other subunit, it is not particularly specific. However, when it bonds to the second subunit of myosin phosphatase, MYPT1 (MW ~130 kDa), this catalytic cleft changes configuration. This results in a dramatic increase in myosin specificity.^[1] Thus, it is clear that MYPT1 has great regulatory power over PP1 and myosin phosphatase, even without the presence of other activators or inhibitors.

The third subunit, M20 (not to be confused with MLC₂₀, the critical regulatory subunit of myosin), is the smallest and most mysterious subunit. Currently little is known about M20, except that it is not necessary for catalysis, as removing the subunit does not affect turnover or selectivity.^[1] While some believe it could have regulatory function, nothing has been determined yet.^[2]

Mechanism

The mechanism of PP1 for myosin phosphatase, with critical enzyme residues shown.^[8]^[9] The substrates and products are bold and in red, and the manganese ions are in blue. The alcohol group shown on myosin after dephosphorylation is the alcohol on Ser-19.

The mechanism of removing the phosphate from Ser-19 is very similar to other dephosphorylation reactions in the cell, such as the activation of glycogen synthase. Myosin's regulatory subunit MLC₂₀ binds to both the hydrophobic and acid grooves of PP1 and MYPT1, the regulatory site on myosin phosphatase.^[1]^[10] Once in the proper configuration, both the phyosphorylated serine and a free water molecule are stabilized by the hydrogen-bonding residues in the active site, as well as the positively charged ions (which interact strongly with the negative phosphate group). His-125 (on myosin phosphatase) donates a proton to Ser-19 MLC₂₀), and the water molecule attacks the phosphorus atom. After shuffling protons to stabilize (which happens rapidly compared to the attack on phosphorus), the phosphate and alcohol are formed, and both leave the active site.

Regulation and Human Health

The regulatory pathways of MLC kinase have been well-established, but until the late 1980s, it was assumed that myosin phosphatase was not regulated, and contraction/relaxation was entirely dependent on MLC kinase activity.^[2] However, since the 1980s, the inhibiting effect of rho-associated protein kinase has been discovered and thoroughly investigated.^[11] RhoA GTP activates Rho-kinase, which phosphorylates the MYPT1 at two major inhibitory sites, Thr-696 and Thr-866.^[12]^[13] This fully demonstrates the value of the MYPT1, not only to increase reaction rate and specificity, but also to greatly slow down the reaction. However, when telokin is added, it effectively undoes the effect of Rho-kinase, even though it does not dephosphorylate MYPT1.^[12]

One other proposed regulatory strategy involves arachidonic acid. When arachidonic acid is added to tensed muscle tissue, the acid decreases the rate of dephosphorylation (and thus relaxation) of myosin. However, it is unclear how arachidonic acid functions as an inhibitor.^[4] Two competing theories are that either arachidonic acid acts as a co-messanger in the rho-kinase cascade mentioned above, or that it binds to the c-terminal of MYPT1.^[4]

When the regulatory systems of myosin phosphatase begin to fail, there can be major health consequences. Since smooth muscle is found in the respiratory, circulatory, and reproductive systems of humans (as well as other places), if the smooth muscle can no longer relax because of faulty regulation, then a wide number of problems ranging from asthma, hypertension, and erectile dysfunction can result.^[4]^[14]

References

^ ^a ^b ^c ^d ^e Terrak, Mohammed; Kerff, Frederic et al. (June 17, 2004). "Structural Basis of Protein Phosphatase 1 Regulation". Nature (429): 780–4. Retrieved 9 March 2015.
^ ^a ^b ^c Hartshorne, DJ; Ito, M (May 1998). "Myosin Light Chain Phosphatase: Subunit Composition, Interactions and Regulation". J Muscle Res Cell Motil. 4: 325–41. Retrieved 9 March 2015.
^ Page 174 in: The vascular smooth muscle cell: molecular and biological responses to the extracellular matrix. Authors: Stephen M. Schwartz, Robert P. Mecham. Editors: Stephen M. Schwartz, Robert P. Mecham. Contributors: Stephen M. Schwartz, Robert P. Mecham. Publisher: Academic Press, 1995. ISBN 0-12-632310-0, ISBN 978-0-12-632310-8
^ ^a ^b ^c ^d Webb, R. Clinton (November 2003). "Smooth Muscle Contraction and Relaxation". Advances in Physiology Education 27 (4): 201–6. Retrieved 9 March 2015.
^ Hurley, Thomas; Yang, Jie et al. (July 18, 2007). "Structural Basis for Regulation of Protein Phosphatase 1 by Inhibitor-2". J. Biol. Chem. 282 (39): 28874–83. doi:10.1074/jbc.m703472200. Retrieved 9 March 2015.
^ Cohen, Patricia T. W. (January 15, 2002). "Protein Phosphatase 1-Targeted in Many Directions". J Cell Sci 115 (2): 780–4. Retrieved March 9, 2015.
^ Fujioka, M; Takahashi, N (April 1, 1998). "A New Isoform of Human Myosin Phosphatase Targeting/Regulatory Subunit (MYPT2): cDNA Cloning, Tissue Expression, and Chromosomal Mapping". Genomics 49 (1): 325–41. Retrieved 9 March 2015.
^ Shi, Yigong (October 30, 2009). "Serine/Threonine Phosphatases: Mechanism through Structure". Cell 139 (3): 468–84. doi:10.1016/j.cell.2009.10.006. Retrieved 9 March 2015.
^ Lee, Ernest Y.C.; Zhang, Lifang et al. (March 15, 1999). "Phosphorylase Phosphatase: New Horizons for an Old Enzyme". Frontiers of Bioscience 4: 270–85. Retrieved March 9, 2015.
^ Gomperts, Bastein D. (August 19, 2009). Signal Transduction: 2nd Edition. London: Academic Press. ISBN 0123694418.
^ Wang, Yuepeng; Riddick, Nadeen et al. (February 27, 2009). "Wang Y, Zheng XR, Riddick N, et al. ROCK Isoform Regulation of Myosin Phosphatase and Contractility in Vascular Smooth Muscle Cells.". Circ. Res 104 (4): 531–40. doi:10.1161/circresaha.108.188524. Retrieved March 9, 2015.
^ ^a ^b Khromov, ES; Momotani, K. et al. (April 27, 2012). "Molecular Mechanism of Telokin-Mediated Disinhibition of Myosin Light Chain Phosphatase and cAMP/cGMP-Induced Relaxation of Gastrointestinal Smooth Muscle". J Biol Chem. 287 (25): 20975–85. doi:10.1074/jbc.m112.341479. Retrieved March 9, 2015.
^ Somlyo, Andrew P.; Somlyo, Avril V. (November 10, 1999). "Signal Transduction by G-Proteins, Rho-Kinase and Protein Phosphatase to Smooth Muscle and Non-Muscle Myosin II". Journal of Physiology 522 (2): 177–85. doi:10.1111/j.1469-7793.2000.t01-2-00177.x. Retrieved March 9, 2015.
^ Aguilar, Hector; Mitchell, B.F. (May 7, 2010). "Physiological Pathways and Molecular Mechanisms Regulating Uterine Contractility". Human Reproduction Update 16 (6): 725–44. doi:10.1093/humupd/dmq016. Retrieved March 9, 2015.

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English Journal

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The protein prostate-apoptosis response (Par)-4 has been implicated in the regulation of smooth muscle contraction, based largely on studies with the A7r5 cell line. A mechanism has been proposed whereby Par-4 binding to MYPT1 (the myosin-targeting subunit of myosin light chain phosphatase, MLCP) bl
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Identification of alkylbenzene sulfonate surfactants leaching from an acrylonitrile butadiene rubber as novel inhibitors of calcineurin activity.

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Calcineurin (CN) is a Ca(2+)/calmodulin (CaM) dependent serine/threonine protein phosphatase and plays important role in several cellular functions in both higher and lower eukaryotes. Here we report inhibition of CN by linear alkylbenzene sulfonate. The clue to the finding was obtained while identi
PMID 23649261

Japanese Journal

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Takeya Kosuke,Wang Xuemei,Sutherland Cindy,Kathol Iris,Loutzenhiser Kathy,Loutzenhiser Rodger D.,Walsh Michael P.
Journal of Smooth Muscle Research 50(0), 18-28, 2014
… publisherSmooth muscle contraction is activated primarily by phosphorylation at Ser19 of the regulatory light chain subunits (LC20) of myosin II, catalysed by Ca(2+)/calmodulin-dependent myosin light chain kinase. …
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Irradiation-tolerant lung cancer cells acquire invasive ability dependent on dephosphorylation of the myosin regulatory light chain

Ishihara Seiichiro,Yasuda Motoaki,Nishioka Takeshi,Mizutani Takeomi,Kawabata Kazushige,Shirato Hiroki,Haga Hisashi
FEBS Letters 587(6), 732-736, 2013-03-18
… This study shows that irradiation-tolerant lung adenocarcinoma demonstrates high invasive capability depending on dephosphorylation of the myosin regulatory light chain (MRLC). … In addition, inhibition of MRLC phosphatase activity decreased the invasive activity. …
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Identification of Alkylbenzene Sulfonate Surfactants Leaching from an Acrylonitrile Butadiene Rubber as Novel Inhibitors of Calcineurin Activity

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NAID 130004054077

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リンク元	「myosin phosphatase」「ミオシン軽鎖ホスファターゼ」
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「myosin phosphatase」

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Myosin Light-Chain Phosphatase
	Structure of complex between PP1 and a portion of MYPT1, generated from 1s70
Identifiers
EC number	3.1.3.53
CAS number	86417-96-1
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
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PMC	articles
PubMed	articles
NCBI	proteins