In
enzymology, an elongation factor 2 kinase () 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
catalyzes the
chemical reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
:
:ATP +
longation factor 2 ADP +
longation factor 2phosphate.
Thus, the two
substrates of this enzyme are
ATP and
elongation factor 2, whereas its two
products
Product may refer to:
Business
* Product (business), an item that serves as a solution to a specific consumer problem.
* Product (project management), a deliverable or set of deliverables that contribute to a business solution
Mathematics
* Produ ...
are
adenosine diphosphate (ADP) and elongation factor 2 phosphate.
Nomenclature
This enzyme belongs to the family of
transferase
A transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds of ...
s, specifically those transferring a phosphate group to the sidechain
oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
atom of
serine or
threonine residues in
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s (
protein-serine/threonine kinases). The
systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature.
A semisystematic name or semitrivial ...
of this enzyme class is "ATP:
longation factor 2phosphotransferase". Other names in common use include Ca/CaM-kinase III, calmodulin-dependent protein kinase III, CaM kinase III, eEF2 kinase, eEF-2K, eEF2K, EF2K, and STK19.
Function
The only known physiological substrate of eEF-2K is eEF-2. Phosphorylation of eEF-2 at Thr-56 by eEF-2K leads to inhibition of the elongation phase of protein synthesis. Phosphorylation of Thr-56 is thought to reduce the affinity of eEF-2 for the ribosome, thereby slowing down the overall rate of elongation.
However, there is growing evidence to suggest that translation of certain mRNAs is actually increased by phosphorylation of eEF-2 by eEF-2K, especially in a neuronal context.
Activation
The activity of eEF-2K is dependent on calcium and calmodulin. Activation of eEF-2K proceeds by a sequential two-step mechanism. First, calcium-calmodulin binds with high affinity to activate the kinase domain, triggering rapid autophosphorylation of Thr-348.
In the second step, autophosphorylation of Thr-348 leads to a conformational change in the kinase likely supported by the binding of phospho-Thr-348 to an allosteric phosphate binding pocket in the kinase domain. This increases the activity of eEF-2K against its substrate, elongation factor 2.
eEF-2K can gain calcium-independent activity through autophosphorylation of Ser-500. However, calmodulin must remain bound to the enzyme for its activity to be sustained.
Cancer
eEF-2K expression is often upregulated in cancer cells, including breast and pancreatic cancers and promotes cell proliferation, survival, motility/migration, invasion and tumorigenesis.
References
Further reading
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EC 2.7.11
Enzymes of unknown structure
{{2.7-enzyme-stub