IκB kinase
Encyclopedia
The IκB kinase 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 signal
s (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.
that catalyzes
the chemical reaction
:
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 transferase
s, specifically those transferring a phosphate group to the sidechain oxygen
atom of serine
or threonine
residues in protein
s (protein-serine/threonine kinases). The systematic name of this enzyme class is ATP:[IkappaB protein] phosphotransferase.
The α- and β-subunits together are catalytically active whereas the γ-subunit serves a regulatory function.
: 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.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
complex that is involved in propagating the cellular response to inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
.
The IκB kinase enzyme complex is part of the upstream NF-κB signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
cascade. The IκBα (inhibitor of kappa B) protein inactivates the NF-κB transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
by masking the nuclear localization signal
Nuclear localization signal
A nuclear localization signal or sequence is an amino acid sequence which 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different...
s (NLS) of NF-κB proteins and keeping them sequestered in an inactive state in the cytoplasm. IKK specifically, phosphorylates
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
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 enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that catalyzes
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
the chemical reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
:
- ATP + IkappaB protein
ADP + IkappaB phosphoprotein
Thus, the two substrates
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
of this enzyme are ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
and IkappaB protein, whereas its two products
Product (chemistry)
Product are formed during chemical reactions as reagents are consumed. Products have lower energy than the reagents and are produced during the reaction according to the second law of thermodynamics. The released energy comes from changes in chemical bonds between atoms in reagent molecules and...
are ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
and IkappaB phosphoprotein.
This enzyme belongs to the family of transferase
Transferase
In biochemistry, a transferase is an enzyme that catalyzes the transfer of a functional group from one molecule to another . For example, an enzyme that catalyzed this reaction would be a transferase:In this example, A would be the donor, and B would be the acceptor...
s, specifically those transferring a phosphate group to the sidechain oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
atom of serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
or threonine
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
residues in protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s (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 IKK1CHUKInhibitor of nuclear factor kappa-B kinase subunit alpha also known as IKK1 or conserved helix-loop-helix ubiquitous kinase is a protein kinase that in humans is encoded by the CHUK gene. IKK-α is part of the IκB kinase complex that plays an important role in regulating the NF-κB transcription...
) - IKK-β (also known as IKK2IKK2IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a protein that in humans is encoded by the IKBKB gene.- Function :...
) - IKK-γ (also known as NEMOIKBKGNF-kappa-B essential modulator also known as inhibitor of nuclear factor kappa-B kinase subunit gamma is a protein that in humans is encoded by the IKBKG gene. NEMO is a subunit of the IκB kinase that activates NF-κB. The human gene for IKBKG is located on chromosome Xq28...
)
The α- and β-subunits together are catalytically active whereas the γ-subunit serves a regulatory function.
Clinical significance
This enzyme participates in 15 pathways related to metabolismMetabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
: MapK signaling
MAPK/ERK pathway
The MAPK/ERK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a growth factor binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a...
, apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, 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
Helicobacter pylori
Helicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...
, pancreatic cancer
Pancreatic cancer
Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...
, prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, chronic myeloid leukemia, acute myeloid leukemia
Acute myeloid leukemia
Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
, and small cell lung cancer.