Eukaryotic elongation factor-2 kinase (eEF-2 kinase or eEF-2K), also known as calmodulin-dependent protein kinase III (CAMKIII) and calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase, [5] is an enzyme that in humans is encoded by the EEF2K gene. [6] [7]
eEF-2 kinase is a highly conserved protein kinase in the calmodulin-mediated signaling pathway that links multiple up-stream signals to the regulation of protein synthesis. It phosphorylates eukaryotic elongation factor 2 (EEF2) and thus inhibits the EEF2 function. [6] [8]
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. [9] [10] 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. [10]
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. [9]
The activity of this kinase is increased in many cancers and may be a valid target for anti-cancer treatment. [6] [11]
It is also suggested that eEF-2K may play a role the rapid anti-depressant effects of ketamine through its regulation of neuronal protein synthesis. [12]
eEF-2K expression is often upregulated in cancer cells, including breast and pancreatic cancers and promotes cell proliferation, survival, motility/migration, invasion and tumorigenesis. [13] [14]
Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the binding of Ca2+ is required for the activation of calmodulin. Once bound to Ca2+, calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases.
CAMK, also written as CaMK or CCaMK, is an abbreviation for the Ca2+/calmodulin-dependent protein kinase class of enzymes. CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca2+) and calmodulin. When activated, the enzymes transfer phosphates from ATP to defined serine or threonine residues in other proteins, so they are serine/threonine-specific protein kinases. Activated CAMK is involved in the phosphorylation of transcription factors and therefore, in the regulation of expression of responding genes. CAMK also works to regulate the cell life cycle (i.e. programmed cell death), rearrangement of the cell's cytoskeletal network, and mechanisms involved in the learning and memory of an organism.
Ca2+
/calmodulin-dependent protein kinase II is a serine/threonine-specific protein kinase that is regulated by the Ca2+
/calmodulin complex. CaMKII is involved in many signaling cascades and is thought to be an important mediator of learning and memory. CaMKII is also necessary for Ca2+
homeostasis and reuptake in cardiomyocytes, chloride transport in epithelia, positive T-cell selection, and CD8 T-cell activation.
Calmodulin 1 is a protein that in humans is encoded by the CALM1 gene.
Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMKIIα), a.k.a.Ca2+/calmodulin-dependent protein kinase II alpha, is one subunit of CamKII, a protein kinase (i.e., an enzyme which phosphorylates proteins) that in humans is encoded by the CAMK2A gene.
Calcium/calmodulin-dependent protein kinase type II beta chain is an enzyme that in humans is encoded by the CAMK2B gene.
Elongation factor 1-delta is a protein that in humans is encoded by the EEF1D gene.
Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.
Calcium/calmodulin-dependent protein kinase type II gamma chain is an enzyme that in humans is encoded by the CAMK2G gene.
Elongation factor 1-alpha 1 (eEF1a1) is a translation elongation protein, expressed across eukaryotes. In humans, it is encoded by the EEF1A1 gene.
In enzymology, an elongation factor 2 kinase is an enzyme that catalyzes the chemical reaction:
Proto-oncogene tyrosine-protein kinase FER is an enzyme that in humans is encoded by the FER gene.
Calcium/calmodulin-dependent protein kinase type 1 is an enzyme that in humans is encoded by the CAMK1 gene.
Elongation factor 1-beta is a protein that in humans is encoded by the EEF1B2 gene.
Eukaryotic elongation factor 2 is a protein that in humans is encoded by the EEF2 gene. It is the archaeal and eukaryotic counterpart of bacterial EF-G.
Elongation factor 1-gamma is a protein that in humans is encoded by the EEF1G gene.
Elongation factor 1-alpha 2 is a protein that in humans is encoded by the EEF1A2 gene.
Calcium/calmodulin-dependent protein kinase kinase 2 is an enzyme that in humans is encoded by the CAMKK2 gene.
The Akt signaling pathway or PI3K-Akt signaling pathway is a signal transduction pathway that promotes survival and growth in response to extracellular signals. Key proteins involved are PI3K and Akt.
Alexey G. Ryazanov is a USSR-born scientist who discovered protein alpha-kinases, professor of Pharmacology at Rutgers University. The team led by Ryazanov discovered a new class of protein kinases — alpha-kinases. One of the alpha-kinases, elongation factor-2 kinase, can regulate the global protein synthesis rate and is implicated in cancer and aging.
Aliases for EEF2K Gene
Eukaryotic Elongation Factor 2 Kinase
Calcium/Calmodulin-Dependent Eukaryotic Elongation Factor 2 Kinase
EEF-2 Kinase
EC 2.7.11.20
EEF-2K
Calcium/Calmodulin-Dependent Eukaryotic Elongation Factor-2 Kinase
Calmodulin-Dependent Protein Kinase III
