IκB kinase

IkappaB kinase
Identifiers
EC number	2.7.11.10
CAS number	159606-08-3
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
Search PMC articles PubMed articles NCBI proteins

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. NF-κB, which is now free migrates into the nucleus and activates the expression of at least 150 genes; some of which are anti-apoptotic.

Catalyzed reaction

In enzymology, an IkappaB kinase (EC 2.7.11.10) 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:

• IKK-α (also known as IKK1) (CHUK)
• IKK-β (also known as IKK2) (IKBKB)
• IKK-γ (also known as NEMO) (IKBKG)

The α- and β-subunits together are catalytically active whereas the γ-subunit serves a regulatory function.

conserved helix-loop-helix ubiquitous kinase Identifiers Symbol CHUK Alt. symbols IKK-alpha, IKK1, TCF16 Entrez 1147 HUGO 1974 OMIM 600664 RefSeq NM_001278 UniProt O15111 Other data EC number 2.7.11.10 Locus Chr. 10 q24-q25

inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta Identifiers Symbol IKBKB Alt. symbols IKK-beta, IKK2 Entrez 3551 HUGO 5960 OMIM 603258 RefSeq NM_001556 UniProt O14920 Other data EC number 2.7.11.10 Locus Chr. 8 p11.2

inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma Identifiers Symbol IKBKG Alt. symbols IKK-gamma, NEMO, IP2, IP1 Entrez 8517 HUGO 5961 OMIM 300248 RefSeq NM_003639 UniProt Q9Y6K9 Other data Locus Chr. X q28

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.

Further reading

• Zandi E, Rothwarf DM, Delhase M, Hayakawa M, Karin M (1997). "The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation". Cell 91 (2): 243–52. doi:10.1016/S0092-8674(00)80406-7. PMID 9346241. 
• Viatour P, Merville MP, Bours V, Chariot A (2005). "Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation". Trends. Biochem. Sci. 30 (1): 43–52. doi:10.1016/j.tibs.2004.11.009. PMID 15653325. 

External links

• I-kappa B Kinase at the US National Library of Medicine Medical Subject Headings (MeSH)