Eukaryotic elongation factor 2 kinase (eEF-2K)

Eukaryotic elongation factor 2 kinase (eEF-2K) is a calcium/calmodulin-dependent threonine protein kinase that negatively regulates the elongation phase of protein synthesis by phosphorylating eukaryotic elongation factor 2 (eEF2), primarily at Thr56, which decreases eEF2's affinity for the ribosome and results in slowed translation elongation[1][3][11]. Belonging to the atypical α-kinase family, eEF-2K is activated by calcium and calmodulin through a two-step activation mechanism involving autophosphorylation at Thr-348 and is subject to regulation by cellular signaling pathways such as mTOR and stress-response cascades[1][2][3][4][11]. It is upregulated in many tumor types and contributes to cancer cell survival, aggressive tumor characteristics, and adaptation to metabolic stress[2][4][8]. eEF-2K also participates in neuronal regulation, learning, memory, and may play a role in the rapid antidepressant response to drugs like ketamine[1][6][9]. Experimental inhibition of eEF-2K has shown anti-tumor effects and reduction in cancer progression in preclinical studies, highlighting its promise as a therapeutic target[4][8]. As of now, only research inhibitors, not approved drugs, directly target eEF-2K in clinical settings.

Other names

calmodulin-dependent protein kinase IIICAMKIIIcalcium/calmodulin-dependent eukaryotic elongation factor 2 kinaseSMEF2K

Inhibition of kinase activity to suppress phosphorylation of eukaryotic elongation factor 2, modulation of protein synthesis rates, potential effects on cell proliferation and survival