CaMK III/eEF-2K

CaMK III/eEF-2K is a calcium/calmodulin-regulated atypical α-kinase that phosphorylates eEF-2 and impedes translation elongation, thereby reducing global protein synthesis^[1][2]. Mechanistically, Ca²⁺/calmodulin activates eEF-2K autophosphorylation at Thr-348 and Ser-500, which regulates substrate phosphorylation and calcium dependence^[3]. Upstream mTOR and MAPK pathways negatively regulate eEF-2K activity, linking nutrient and growth signaling to translational control^[2]. In cancer models, eEF-2K regulates autophagy, apoptosis, angiogenesis, invasion, and metastasis, and supports tumor-cell adaptation to hypoxia, nutrient depletion, and acidosis^[4]. In Akt-inhibited glioma cells, eEF-2K inhibition suppresses autophagy, promotes apoptosis, and reinforces MK-2206 efficacy^[5]. Compared with conventional protein kinases and related CaMK signaling enzymes, eEF-2K is distinguished as an atypical α-kinase and the only calmodulin-dependent member of this family^[1][4]. For experimental applications, recombinant human eEF-2K can be purified from E. coli and phosphorylates wheat-germ eEF-2 with kinetic parameters comparable to mammalian enzyme^[2]. Small-molecule and natural-product eEF-2K inhibitors provide tools for cancer chemotherapy research and structure-activity relationship studies^[4].