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General Information:

Id:	1,150
Diseases:	Parkinson disease
Organism:	Mus musculus
Tissue/Cell line:	BTO:0003292 RAW-264.7 cell
Publication type:	article
Reference:	Matsuzawa A et al.(2005) ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity. Nat. Immunol. 6: 587-592 [PMID: 15864310]

Interaction Information:

Comment	ASK1 was activated by LPS through production of ROS, but only weakly by peptidoglycan in RAW264.7 cells.
Formal Description Interaction-ID: 7498	drug/chemical compound Lipopolysaccharide increases_activity of gene/protein MAP3K5 through production of ROS

Comment	ASK1 is required for LPS-induced p38MAPK activation.
Formal Description Interaction-ID: 7499	drug/chemical compound Lipopolysaccharide increases_activity of gene/protein p38 MAPK in the presence of ASK1

Comment	LPS activates JNK.
Formal Description Interaction-ID: 7500	drug/chemical compound Lipopolysaccharide increases_activity of gene/protein MAPK8
Drugbank entries	Show/Hide entries for MAPK8
Drugbank DB01782	2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One not specified MAPK8
Drugbank DB07218	6-CHLORO-9-HYDROXY-1,3-DIMETHYL-1,9-DIHY ... not specified MAPK8
Drugbank DB07268	2-({2-[(3-HYDROXYPHENYL)AMINO]PYRIMIDIN- ... not specified MAPK8
Drugbank DB07272	N-(4-AMINO-5-CYANO-6-ETHOXYPYRIDIN-2-YL) ... not specified MAPK8
Drugbank DB07276	5-CYANO-N-(2,5-DIMETHOXYBENZYL)-6-ETHOXY ... not specified MAPK8
Drugbank DB07845	2-fluoro-6-{[2-({2-methoxy-4-[(methylsul ... not specified MAPK8

Comment	ASK1 is required for LPS-induced p38MAPK activation.
Formal Description Interaction-ID: 7501	drug/chemical compound Lipopolysaccharide increases_activity of process stress-activated MAPK cascade in the presence of ASK1

Comment	LPS activates NF-kappaB.
Formal Description Interaction-ID: 7502	drug/chemical compound Lipopolysaccharide increases_activity of complex/PPI NF-kappaB complex

Comment	LPS induces NF-kappaB cascade.
Formal Description Interaction-ID: 7503	drug/chemical compound Lipopolysaccharide increases_activity of process I-kappaB kinase/NF-kappaB signaling

Comment	ASK1 is required for LPS-induced p38MAPK activation.
Formal Description Interaction-ID: 7506	gene/protein MAP3K5 increases_activity of gene/protein p38 MAPK after induction with LPS

Comment	LPS-induced production of IL-6, tumor necrosis factor (TNF), nitric oxide and IL-1beta was diminished in ASK1-deficient splenocytes, indicating that ASK1 is required for LPS-induced cytokine production.
Formal Description Interaction-ID: 7507	gene/protein MAP3K5 increases_quantity of gene/protein IL6 after induction with LPS
Drugbank entries	Show/Hide entries for IL6
Drugbank DB01404	Ginseng antagonist IL6
Drugbank DB01404	Ginseng antagonist IL6

Comment	LPS-induced production of IL-6, tumor necrosis factor (TNF), nitric oxide and IL-1beta was diminished in ASK1-deficient splenocytes, indicating that ASK1 is required for LPS-induced cytokine production.
Formal Description Interaction-ID: 7508	gene/protein MAP3K5 increases_quantity of gene/protein TNF after induction with LPS
Drugbank entries	Show/Hide entries for TNF
Drugbank DB00005	Etanercept antibody TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB00608	Chloroquine not specified TNF
Drugbank DB01041	Thalidomide inhibitor TNF
Drugbank DB01296	Glucosamine not specified TNF
Drugbank DB01407	Clenbuterol other/unknown TNF
Drugbank DB01411	Pranlukast other/unknown TNF
Drugbank DB01427	Amrinone inhibitor TNF
Drugbank DB00051	Adalimumab antibody TNF
Drugbank DB00065	Infliximab inhibitor TNF
Drugbank DB01427	Amrinone inhibitor TNF

Comment	LPS-induced production of IL-6, tumor necrosis factor (TNF), nitric oxide and IL-1beta was diminished in ASK1-deficient splenocytes, indicating that ASK1 is required for LPS-induced cytokine production.
Formal Description Interaction-ID: 7509	gene/protein MAP3K5 increases_quantity of gene/protein IL1B after induction with LPS
Drugbank entries	Show/Hide entries for IL1B
Drugbank DB01017	Minocycline modulator IL1B
Drugbank DB05260	Gallium nitrate antagonist IL1B
Drugbank DB06168	Canakinumab not specified IL1B
Drugbank DB06168	Canakinumab not specified IL1B

Comment	LPS-induced production of IL-6, tumor necrosis factor (TNF), nitric oxide and IL-1beta was diminished in ASK1-deficient splenocytes, indicating that ASK1 is required for LPS-induced cytokine production.
Formal Description Interaction-ID: 7510	gene/protein MAP3K5 increases_quantity of drug/chemical compound NO after induction with LPS

Comment	LPS-induced expression of inducible nitric oxide synthase was also reduced in ASK1-deficient DCs, indicating that ASK1 is required for LPS-induced cytokine production.
Formal Description Interaction-ID: 7511	gene/protein MAP3K5 increases_quantity of gene/protein NOS2 after induction with LPS
Drugbank entries	Show/Hide entries for NOS2
Drugbank DB00125	L-Arginine not specified NOS2
Drugbank DB00155	L-Citrulline not specified NOS2
Drugbank DB01110	Miconazole inhibitor NOS2
Drugbank DB01234	Dexamethasone negative modulator NOS2
Drugbank DB01686	N,N-dimethylarginine not specified NOS2
Drugbank DB01835	4r-Fluoro-N6-Ethanimidoyl-L-Lysine not specified NOS2
Drugbank DB01997	3-Bromo-7-Nitroindazole not specified NOS2
Drugbank DB02044	N-(3-(Aminomethyl)Benzyl)Acetamidine not specified NOS2
Drugbank DB02207	7-Nitroindazole not specified NOS2
Drugbank DB02234	Ethylisothiourea not specified NOS2
Drugbank DB02462	Thiocoumarin not specified NOS2
Drugbank DB02533	Aminoguanidine inhibitor NOS2
Drugbank DB02539	S-Ethylisothiourea not specified NOS2
Drugbank DB02644	N-Omega-Propyl-L-Arginine not specified NOS2
Drugbank DB02692	(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin not specified NOS2
Drugbank DB03014	Heme not specified NOS2
Drugbank DB03100	6-Nitroindazole not specified NOS2
Drugbank DB03144	N-Omega-Hydroxy-L-Arginine not specified NOS2
Drugbank DB03271	7,8-Dihydro-L-Biopterin not specified NOS2
Drugbank DB03449	N-(4-(2-((3-Chlorophenylmethyl)Amino)Eth ... not specified NOS2
Drugbank DB03953	L-Thiocitrulline not specified NOS2
Drugbank DB04400	7,8-Dihydrobiopterin not specified NOS2
Drugbank DB04534	5-Nitroindazole not specified NOS2
Drugbank DB06879	5-(4'-AMINO-1'-ETHYL-5',8'-DIFLUORO-1'H- ... not specified NOS2
Drugbank DB06916	N-[2-(1,3-BENZODIOXOL-5-YL)ETHYL]-1-[2-( ... not specified NOS2
Drugbank DB07002	4-({4-[(4-methoxypyridin-2-yl)amino]pipe ... not specified NOS2
Drugbank DB07003	(2S)-2-methyl-2,3-dihydrothieno[2,3-f][1 ... not specified NOS2
Drugbank DB07007	(3R)-3-[(1,2,3,4-tetrahydroisoquinolin-7 ... not specified NOS2
Drugbank DB07008	4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMI ... not specified NOS2
Drugbank DB07011	(3S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-3-[4 ... not specified NOS2
Drugbank DB07029	4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMI ... not specified NOS2
Drugbank DB07306	ETHYL 4-[(4-CHLOROPYRIDIN-2-YL)AMINO]PIP ... not specified NOS2
Drugbank DB07318	N-[2-(4-AMINO-5,8-DIFLUORO-1,2-DIHYDROQU ... not specified NOS2
Drugbank DB07388	ETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIP ... not specified NOS2
Drugbank DB07389	N-[2-(6-AMINO-4-METHYLPYRIDIN-2-YL)ETHYL ... not specified NOS2
Drugbank DB07405	1-(6-CYANO-3-PYRIDYLCARBONYL)-5',8'-DIFL ... not specified NOS2
Drugbank DB08214	4-(1H-IMIDAZOL-1-YL)PHENOL not specified NOS2
Drugbank DB08750	1-[4-(AMINOMETHYL)BENZOYL]-5'-FLUORO-1'H ... not specified NOS2
Drugbank DB08814	Triflusal agonist NOS2
Drugbank DB00125	L-Arginine not specified NOS2
Drugbank DB00155	L-Citrulline not specified NOS2
Drugbank DB01686	N,N-dimethylarginine not specified NOS2
Drugbank DB01835	4r-Fluoro-N6-Ethanimidoyl-L-Lysine not specified NOS2
Drugbank DB01997	3-Bromo-7-Nitroindazole not specified NOS2
Drugbank DB02207	7-Nitroindazole not specified NOS2
Drugbank DB02234	Ethylisothiourea not specified NOS2
Drugbank DB02533	Aminoguanidine inhibitor NOS2
Drugbank DB02539	S-Ethylisothiourea not specified NOS2
Drugbank DB02644	N-Omega-Propyl-L-Arginine not specified NOS2
Drugbank DB02692	(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin not specified NOS2
Drugbank DB03014	Heme not specified NOS2
Drugbank DB03100	6-Nitroindazole not specified NOS2
Drugbank DB03144	N-Omega-Hydroxy-L-Arginine not specified NOS2
Drugbank DB03271	7,8-Dihydro-L-Biopterin not specified NOS2
Drugbank DB03953	L-Thiocitrulline not specified NOS2
Drugbank DB04400	7,8-Dihydrobiopterin not specified NOS2
Drugbank DB04534	5-Nitroindazole not specified NOS2

Comment	LPS is a ligand for TLR4.
Formal Description Interaction-ID: 7512	drug/chemical compound Lipopolysaccharide interacts (colocalizes) with gene/protein TLR4
Drugbank entries	Show/Hide entries for TLR4
Drugbank DB02767	3-Hydroxy-Myristic Acid not specified TLR4
Drugbank DB08231	MYRISTIC ACID not specified TLR4

Comment	ASK1 is selectively required for TLR4-induced cytokine production (e.g. IL-6) via p38.
Formal Description Interaction-ID: 7513	gene/protein TLR4 increases_quantity of gene/protein IL6 after induction with LPS and in the presence of ASK1
Drugbank entries	Show/Hide entries for TLR4 or IL6
Drugbank DB02767	3-Hydroxy-Myristic Acid not specified TLR4
Drugbank DB08231	MYRISTIC ACID not specified TLR4
Drugbank DB01404	Ginseng antagonist IL6
Drugbank DB01404	Ginseng antagonist IL6

Comment	ASK1 is selectively required for TLR4-induced cytokine production (e.g. IL-6) via p38.
Formal Description Interaction-ID: 7518	gene/protein MAP3K5 affects_activity of gene/protein TLR4 in the presence of p38 MAPK
Drugbank entries	Show/Hide entries for TLR4
Drugbank DB02767	3-Hydroxy-Myristic Acid not specified TLR4
Drugbank DB08231	MYRISTIC ACID not specified TLR4

Comment	ASK1 was activated by LPS through production of ROS, but only weakly by peptidoglycan in RAW264.7 cells.
Formal Description Interaction-ID: 7521	drug/chemical compound Peptidoglycan NOT increases_activity of gene/protein MAP3K5

Comment	TRAF6 is an adaptor protein involved in the TLR signaling complex.
Formal Description Interaction-ID: 7524	gene/protein TRAF6 affects_activity of process toll-like receptor signaling pathway

Comment	TRAF6, an adaptor protein involved in the TLR signaling complex, binds and activates ASK1.
Formal Description Interaction-ID: 7526	gene/protein TRAF6 interacts (colocalizes) with gene/protein MAP3K5 after stimulation with ligand or LPS

Comment	TRAF6, an adaptor protein involved in the TLR signaling complex, binds and activates ASK1.
Formal Description Interaction-ID: 7527	gene/protein TRAF6 increases_activity of gene/protein MAP3K5