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EC Tree
The taxonomic range for the selected organisms is: Mus musculus The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
adenosine kinase, adk, ado kinase, adk-l, adk-s, rv2202c, atp:adenosine 5'-phosphotransferase, ldadk,
more
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adenosine kinase (phosphorylating)
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kinase, adenosine (phosphorylating)
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ATP + adenosine = ADP + AMP
mechanism
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phospho group transfer
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ATP:adenosine 5'-phosphotransferase
2-Aminoadenosine can also act as acceptor.
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ATP + adenosine
ADP + AMP
ATP + 6-methylmercaptopurine riboside
ADP + 6-methylmercaptopurine-D-riboside 5'-phosphate
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-
?
ATP + adenosine
ADP + AMP
ATP + cordycepin
ADP + cordycepin 5'-phosphate
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-
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?
CTP + adenosine
CDP + AMP
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CTP is a poor substrate
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?
GTP + adenosine
GDP + AMP
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best substrate
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?
ITP + adenosine
IDP + AMP
UTP + adenosine
UDP + AMP
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UTP is a poor substrate
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?
additional information
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low levels of ADK are essential to maintain adenosine-mediated neuroprotection
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?
ATP + adenosine
ADP + AMP
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?
ATP + adenosine
ADP + AMP
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-
?
ATP + adenosine
ADP + AMP
the major route of myocardial adenosine metabolism. Receptor-independent role of adenosine for adenosine kinase-mediated adenosine metabolism in cardiomyocyte microtubule dynamics and protection against maladaptive hypertrophy
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?
ATP + adenosine
ADP + AMP
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?
ATP + adenosine
ADP + AMP
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?
ATP + adenosine
ADP + AMP
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MgATP2- is the true substrate
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-
?
ATP + adenosine
ADP + AMP
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strictly specific for adenosine
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?
ITP + adenosine
IDP + AMP
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about half as effective as GTP
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?
ITP + adenosine
IDP + AMP
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about half as effective as ATP
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?
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ATP + adenosine
ADP + AMP
additional information
?
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low levels of ADK are essential to maintain adenosine-mediated neuroprotection
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?
ATP + adenosine
ADP + AMP
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?
ATP + adenosine
ADP + AMP
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?
ATP + adenosine
ADP + AMP
the major route of myocardial adenosine metabolism. Receptor-independent role of adenosine for adenosine kinase-mediated adenosine metabolism in cardiomyocyte microtubule dynamics and protection against maladaptive hypertrophy
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?
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K+
allosteric activator, it increases the catalytic turnover (Kcat) but does not affect the affinity of the enzyme for adenosine or ATP
Co2+
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can partially substitute for Mg2+
Fe2+
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activation
Fe2+
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sulfate form is more effective than the chloride form
Mg2+
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requirement
Mg2+
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optimal at Mg: ATP ratio 1
Mg2+
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the chloride form is more effective than the sulfate form
Mn2+
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can partially substitute for Mg2+
Ni2+
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can partially substitute for Mg2+
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2-Phenylethylureidopurine ribonucleoside
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competitive inhibition
5'-amino-5'-deoxy-adenosine
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following systemic administration, adenosine kinase inhibitors can alleviate acute thermal nociception as measured by the hot-plate test in mice
5'-deoxy-5-iodotubercidin
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following systemic administration, adenosine kinase inhibitors can alleviate acute thermal nociception as measured by the hot-plate test in mice
5-iodotubercidin
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following systemic administration, adenosine kinase inhibitors can alleviate acute thermal nociception as measured by the hot-plate test in mice
6-Methylmercaptopurine riboside
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and analogs
6-methylmercaptopurine riboside phosphate
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product inhibition, competitive with respect to ATP and noncompetitive with respect to 6-methylmercaptopurine ribonucleoside
6-Ureidopurine ribonucleosides
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7-beta-D-ribofuranosyl-pyrrolo-(2,3-d)-pyrimidine
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competitive with respect to 6-methylmercaptopurine riboside and noncompetitive with respect to ATP
adenosine
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competitive with respect to 6-methylmercaptopurine riboside
ADP
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product inhibition
ADP
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noncompetitive with respect to ATP and 6-methylmercaptopurine ribonucleoside at low concentrations of the substrates
additional information
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additional information
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no inhibition by polyamines
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bovine serum albumin
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additional information
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no activation by polyamines
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0.00002
adenosine
recombinant isozymes AK-S and AK-L, pH 7.5, 37°C
0.46
3'-deoxyadenosine
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pH 5.8, 25ºC, natural
0.01
6-Methylmercaptopurine riboside
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pH 6.0, 37ºC
additional information
additional information
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kinetic study
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0.00015 - 0.0005
adenosine
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0.0017
adenosine
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pH 6.8, 37ºC, 12 mM ATP and 3 mM MgCl2
0.002
adenosine
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pH 6.8, 37ºC, 1 mM ATP and 0.7 mM MgCl2
0.58
adenosine
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pH 5.8, 25ºC
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0.0004
2-Phenylethylureidopurine ribonucleoside
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-
0.16
6-methylmercaptopurine riboside phosphate
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pH 6.0, 37ºC
0.015
7-beta-D-ribofuranosyl-pyrrolo-(2,3-d)-pyrimidine
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pH 6.0, 37ºC
0.26
adenosine
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pH 6.0, 37ºC
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additional information
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additional information
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additional information
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the pH-optimum is a function of the ATP/Mg2+ ratio
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SwissProt
brenda
isozymes AK-L and AK-S; a long and a short isozyme, i.e. AK-L and AK-S
SwissProt
brenda
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brenda
low expression level
brenda
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brenda
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brenda
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brenda
low expression level
brenda
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brenda
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brenda
low expression level
brenda
-
brenda
highest enzyme expression level
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low expression level
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brain, low expression level
brenda
low expression level
brenda
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brenda
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brenda
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brenda
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brenda
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L1210, implanted in mice
brenda
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brenda
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ADK expression in young neurons may provide a salvage pathway to utilize adenosine in nucleic acid synthesis
brenda
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180 cells
brenda
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expressed most strongly in astrocytes
brenda
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astrocyte-based ADK provides a critical link between astrogliosis and neuronal dysfunction in epilepsy
brenda
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brenda
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at early postnatal stages ADK immunoreactivity is prominent in neurons, notably in cerebral cortex and hippocampus. Thereafter, adenosine kinase gradually disappears from neurons and appears in newly developed nestin- and glial fibrillary acidic protein-positive astrocytes. The region-specific downregulation of neuronal adenosine kinase coincides with the onset of myelination. After postnatal day 14, the transition from neuronal to astrocytic ADK expression is complete, except in a subset of neurons that retain ADK until adulthood in specific regions, such as the striatum
brenda
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low levels of adenosine kinase are essential to maintain adenosine-mediated endogenous neuroprotection and pathologic increases in ADK may render the brain more susceptible to injury
brenda
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transgenic overexpression of adenosine kinase in brain leads to multiple learning impairments and altered sensitivity to psychomimetic drugs
brenda
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transgenic overexpression of ADK, which reduces adenosine in mouse brain, results in increased levels of myelin proteolipid protein
brenda
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brenda
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transient downregulation of hippocampal ADK after stroke might be a protective mechanism during maturation hippocampal cell loss
brenda
additional information
isozyme AK-L and AK-S expression patterns
brenda
additional information
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isozyme AK-L and AK-S expression patterns
brenda
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brenda
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brenda
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malfunction
disruption of adenosine kinase causes spontaneous cardiac hypertrophy
metabolism
the enzyme is involved in myocardial adenosine metabolism. Cardiomyocyte adenosine kinase expression attenuates pressure overload induced hypertrophy. Aadenosine kinase regulates cardiac mTORC1 and p44/42 ERK MAP kinase signaling. Adenosine metabolism by adenosine kinase diminishes detyrosinated microtubules
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ADK_MOUSE
361
0
40149
Swiss-Prot
other Location (Reliability: 1 )
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43500
x * 45000, recombinant His-tagged isozyme AK-L, SDS-PAGE, x * 43500, recombinant His-tagged isozyme AK-S, SDS-PAGE
45000
x * 45000, recombinant His-tagged isozyme AK-L, SDS-PAGE, x * 43500, recombinant His-tagged isozyme AK-S, SDS-PAGE
56000
-
PAGE, sucrose density gradient centrifugation, gel filtration
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?
x * 45000, recombinant His-tagged isozyme AK-L, SDS-PAGE, x * 43500, recombinant His-tagged isozyme AK-S, SDS-PAGE
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phosphoprotein
the recombinant isozymes AK-L and AK-S became phosphorylated by protein kinase C, no significant phosphorylation level by protein kinases PKA, PKG, MAPK, CK2, and Cdk1, overview
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sitting drop vapor diffusion method, crystal structures of binary complex with adenosine at 1.2 A and of ternary complex with ADP and adenosine at 1.8 A
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D310A
catalytically deficient mutant that looses responsiveness to K+
D310P
catalytically deficient mutant that looses responsiveness to K+
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7.4
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t1/2: 45 min at 37°C
641078
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25 - 37
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60 min stable at pH 6.8
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bovine serum albumin stabilizes
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-18°C, in 20% glycerol, at least 6 months
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-20°C, in 45% sucrose, at least 1 month
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-20°C, partially purified, 1 year
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recombinant His-tagged isozymes AK-L and AK-S from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
ammonium sulfate fractionation and gel filtration, 15-20fold purification
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chromatography on Sephadex G-100
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streptomycin sulfate and ammonium sulfate fractionation, chromatography on DEAE-cellulose and affinity chromatography
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2 isozymes AK-L and AK-S, DNA and amino acid sequence determination and analysis, overexpression of His-tagged proteins in Escherichia coli strain BL21(DE3)
expression in Escherichia coli BL21(DE3)
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medicine
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the enzyme is a rational therapeutic target to enhance neuroprotection in ischemia
medicine
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astrocyte-based ADK provides a critical link between astrogliosis and neuronal dysfunction in epilepsy
medicine
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pathologic overexpression of ADK as in epilepsy may also render the brain more susceptible to injury from ischemia. Consequently, ADK emerges as a rational therapeutic target to enhance neuroprotection
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Divekar, A.Y.; Hakala, M.T.; Chheda, G.B.; Hong, C.I.
6-Ureido derivatives of 9-(-D-ribofuranosyl)purine as inhibitors of adenosine kinase
Biochem. Pharmacol.
22
545-548
1973
Mus musculus
brenda
Lindberg, B.; Klenow, H.; Hansen, K.
Some properties of partially purified mammalian adenosine kinase
J. Biol. Chem.
242
350-356
1967
Oryctolagus cuniculus, Mus musculus
brenda
Chang, C.H.; Brockman, R.W.; Bennett, L.L.
Adenosine kinase from L1210 cells. Purification and some properties of the enzyme
J. Biol. Chem.
255
2366-2371
1980
Mus musculus
brenda
Henderson, J.F.; Mikoshiba, A.; Chu, S.Y.; Caldwell, I.C.
Kinetic studies of adenosine kinase from Ehrlich ascites tumor cells
J. Biol. Chem.
247
1972-1975
1972
Mus musculus
brenda
Sahin, B.; Kansy, J.W.; Nairn, A.C.; Spychala, J.; Ealick, S.E.; Fienberg, A.A.; Greene, R.W.; Bibb, J.A.
Molecular characterization of recombinant mouse adenosine kinase and evaluation as a target for protein phosphorylation
Eur. J. Biochem.
271
3547-3555
2004
Mus musculus (P55264), Mus musculus
brenda
Matulenko, M.A.; Paight, E.S.; Frey, R.R.; Gomtsyan, A.; DiDomenico, S.; Jiang, M.; Lee, C.H.; Stewart, A.O.; Yu, H.; Kohlhaas, K.L.; Alexander, K.M.; McGaraughty, S.; Mikusa, J.; Marsh, K.C.; Muchmore, S.W.; Jakob, C.L.; Kowaluk, E.A.; Jarvis, M.F.; Bhagwat, S.S.
4-amino-5-aryl-6-arylethynylpyrimidines: structure-activity relationships of non-nucleoside adenosine kinase inhibitors
Bioorg. Med. Chem.
15
1586-1605
2007
Mus musculus
brenda
Pignataro, G.; Maysami, S.; Studer, F.E.; Wilz, A.; Simon, R.P.; Boison, D.
Downregulation of hippocampal adenosine kinase after focal ischemia as potential endogenous neuroprotective mechanism
J. Cereb. Blood Flow Metab.
28
17-23
2007
Mus musculus
brenda
Studer, F.E.; Fedele, D.E.; Marowsky, A.; Schwerdel, C.; Wernli, K.; Vogt, K.; Fritschy, J.M.; Boison, D.
Shift of adenosine kinase expression from neurons to astrocytes during postnatal development suggests dual functionality of the enzyme
Neuroscience
142
125-137
2006
Mus musculus
brenda
Yee, B.K.; Singer, P.; Chen, J.F.; Feldon, J.; Boison, D.
Transgenic overexpression of adenosine kinase in brain leads to multiple learning impairments and altered sensitivity to psychomimetic drugs
Eur. J. Neurosci.
26
3237-3252
2007
Mus musculus
brenda
Pignataro, G.; Simon, R.P.; Boison, D.
Transgenic overexpression of adenosine kinase aggravates cell death in ischemia
J. Cereb. Blood Flow Metab.
27
1-5
2007
Mus musculus
brenda
Li, T.; Ren, G.; Lusardi, T.; Wilz, A.; Lan, J.Q.; Iwasato, T.; Itohara, S.; Simon, R.P.; Boison, D.
Adenosine kinase is a target for the prediction and prevention of epileptogenesis in mice
J. Clin. Invest.
118
571-582
2008
Mus musculus
brenda
Wu, N.L.; Boison, D.
Adenosine kinase expression modulates expression of myelin proteolipid protein
Open Neurosci. J.
1
15-19
2007
Mus musculus
-
brenda
Fassett, J.; Xu, X.; Kwak, D.; Zhu, G.; Fassett, E.K.; Zhang, P.; Wang, H.; Mayer, B.; Bache, R.J.; Chen, Y.
Adenosine kinase attenuates cardiomyocyte microtubule stabilization and protects against pressure overload-induced hypertrophy and LV dysfunction
J. Mol. Cell. Cardiol.
130
49-58
2019
Mus musculus (P55264)
brenda
de Oliveira, R.R.; Morales-Neto, R.; Rocco, S.A.; Sforca, M.L.; Polo, C.C.; Tonoli, C.C.C.; Mercaldi, G.F.; Cordeiro, A.T.; Murakami, M.T.; Franchini, K.G.
Adenosine kinase couples sensing of cellular potassium depletion to purine metabolism
Sci. Rep.
8
11988
2018
Mus musculus (P55264), Mus musculus
brenda