Mitogen-activated protein kinase kinase kinase 8 is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that in humans is encoded by the ''MAP3K8''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Function
The gene was identified by its oncogenic transforming activity in cells. The encoded protein is a member of the
serine/threonine-specific protein kinase
A serine/threonine protein kinase () is a kinase enzyme, in particular a protein kinase, that phosphorylates the OH group of the amino-acid residues serine or threonine, which have similar side chains. At least 350 of the 500+ human prot ...
family. This kinase can activate
ERK1
Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the ''MAPK3'' gene.
Function
The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) famil ...
,
ERK2 and
p38 MAP kinases
p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell different ...
.
This kinase was shown to activate
IkappaB kinases, and thus induce the nuclear production of
NF-kappaB. This kinase was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. Studies of a similar gene in rat suggested the direct involvement of this kinase in the proteolysis of NF-kappaB1, p105 (NFKB1). This gene may also start transcription at a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity.
In mice, the gene is known as TPL2 and is a tumor-suppressor gene whose absence contributes to the development and progression of cancer. However, it functions in other organs as a oncogene, promoting cancer.
Interactions
MAP3K8 has been shown to
interact
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with
AKT1
RAC(Rho family)-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the ''AKT1'' gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) protein domains. It ...
,
,
NFKB2
Nuclear factor NF-kappa-B p100 subunit is a protein that in humans is encoded by the ''NFKB2'' gene.
Function
NF-κB has been detected in numerous cell types that express cytokines, chemokines, growth factors, cell adhesion molecules, and some ...
,
NFKB1
Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the ''NFKB1'' gene.
This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD prot ...
,
References
Further reading
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EC 2.7.11