IκB kinase

The IκB kinase (IKK) is an enzyme complex that is involved in propagating the cellular response to inflammation.

The IκB kinase enzyme complex is part of the upstream NF-κB signal transduction cascade. The IκBα (inhibitor of kappa B) protein inactivates the NF-κB transcription factor by masking the nuclear localization signals (NLS) of NF-κB proteins and keeping them sequestered in an inactive state in the cytoplasm. IKK specifically, phosphorylates the inhibitory IκBα protein. This phosphorylation results in the dissociation of IκBα from NF-κB and thereby activates NF-κB.

Catalyzed reaction
In enzymology, an IkappaB kinase is an enzyme that catalyzes the chemical reaction:


 * ATP + IkappaB protein $$\rightleftharpoons$$ ADP + IkappaB phosphoprotein

Thus, the two substrates of this enzyme are ATP and IkappaB protein, whereas its two products are ADP and IkappaB phosphoprotein.

This enzyme belongs to the family of transferases, specifically those transferring a phosphate group to the sidechain oxygen atom of serine or threonine residues in proteins (protein-serine/threonine kinases). The systematic name of this enzyme class is ATP:[IkappaB protein] phosphotransferase.

Structure
The IκB kinase complex is composed of three subunits each encoded by a separate gene: The α- and β-subunits together are catalytically active whereas the γ-subunit serves a regulatory function.
 * IKK-α (also known as IKK1)
 * IKK-β (also known as IKK2)
 * IKK-γ (also known as NEMO)

Clinical significance
This enzyme participates in 15 pathways related to metabolism: MapK signaling, apoptosis, Toll-like receptor signaling, T cell receptor signaling, B cell receptor signaling, insulin signaling, adipocytokine signaling, Type 2 diabetes mellitus, epithelial cell signaling in helicobacter pylori, pancreatic cancer, prostate cancer, chronic myeloid leukemia, acute myeloid leukemia, and small cell lung cancer.