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Literature summary for 2.7.11.10 extracted from

  • Dzamko, N.; Inesta-Vaquera, F.; Zhang, J.; Xie, C.; Cai, H.; Arthur, S.; Tan, L.; Choi, H.; Gray, N.; Cohen, P.; Pedrioli, P.; Clark, K.; Alessi, D.R.
    The IkappaB kinase family phosphorylates the Parkinsons disease kinase LRRK2 at Ser935 and Ser910 during Toll-like receptor signaling (2012), PLoS ONE, 7, e39132.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression of the enzyme using the baculovirus transfection method in HEK-293 cells Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
BI605906 an IKKbeta inhibitor Mus musculus
additional information two structurally unrelated kinase inhibitors, termed NG25 or 5Z-7-oxozeaenol, inhibit the TAK1 protein kinase, and therefore also inhibit activation of IKKalpha and IKKbeta Mus musculus
MRT67307 an IKKepsilon/TBK1 kinase inhibitor Mus musculus

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + [IRF3 protein] Mus musculus phosphorylation at Ser396 by IKK-related IKKepsilon and TBK1 kinase ADP + [IRF3 phosphoprotein]
-
?
ATP + [leucine-rich repeat kinase 2 protein] Mus musculus catalyzed reaction of canonical IKKalpha and IKKbeta and IKK-related IKKepsilon and TBK1 kinase ADP + [leucine-rich repeat kinase 2 phosphoprotein]
-
?
ATP + [optineurin protein] Mus musculus phosphorylation at Ser177 by IKK-related IKKepsilon and TBK1 kinase ADP + [optineurin phosphoprotein]
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
macrophage bone marrow-derived or RAW-264.7 macrophages Mus musculus
-
RAW-264.7 cell
-
Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + [IRF3 protein] phosphorylation at Ser396 by IKK-related IKKepsilon and TBK1 kinase Mus musculus ADP + [IRF3 phosphoprotein]
-
?
ATP + [leucine-rich repeat kinase 2 protein] catalyzed reaction of canonical IKKalpha and IKKbeta and IKK-related IKKepsilon and TBK1 kinase Mus musculus ADP + [leucine-rich repeat kinase 2 phosphoprotein]
-
?
ATP + [leucine-rich repeat kinase 2 protein] phosphorylation of LRRK2 at Ser910 and Ser935 by IKKalpha and IKKbeta Mus musculus ADP + [leucine-rich repeat kinase 2 phosphoprotein]
-
?
ATP + [optineurin protein] phosphorylation at Ser177 by IKK-related IKKepsilon and TBK1 kinase Mus musculus ADP + [optineurin phosphoprotein]
-
?

Synonyms

Synonyms Comment Organism
IKKalpha
-
Mus musculus
IKKbeta
-
Mus musculus
IKKepsilon
-
Mus musculus
LRRK2 kinase
-
Mus musculus
TBK1 kinase
-
Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
assay at Mus musculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Mus musculus

Cofactor

Cofactor Comment Organism Structure
ATP
-
Mus musculus

Expression

Organism Comment Expression
Mus musculus LRRK2 phoshorylation is not induced by activation of the MyD88 pathway additional information
Mus musculus Zymosan induces LRRK2 phosphorylation at S395 by IKK, stimulation of the Toll-like receptor pathway by MyD88-dependent agonists in bone marrow-derived macrophages or RAW264.7 macrophages induces IKK up

General Information

General Information Comment Organism
metabolism LRRK2 does not play a major role in regulating the secretion of inflammatory cytokines induced by activation of the MyD88 pathway and LRRK2 kinase activity is not required for TLR-mediated Ser935 phosphorylation Mus musculus
physiological function IKK catalyzes phosphorylation of LRRK2 at Ser910 and Ser935, the phosphorylation sites that regulate the binding of protein 14-3-3 to LRRK2. Phosphorylation of LRRK2 by IKKs plays in controlling macrophage biology. But increased phosphorylation of Ser910 and Ser935 induced by activation of the MyD88 pathway is insensitive to LRRK2 kinase inhibitors Mus musculus