Increased activity of the eEF-2 specific, Ca2+ and calmodulin dependent protein kinase III during the S-phase in ehrlich ascites cells

Carlberg, U.; Nilsson, Anders; Skog, Sven; Palmquist, Kim; Nygård, Odd

doi:10.1016/s0006-291x(05)81347-6

Cited by 17 publications

(12 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Figure 4 demonstrates that the activity of CaM kinase III per cell increased two-to threefold in non-synchronized S-phase cells. The data are similar to those of Carlberg et al (1991), who also found that CaM kinase III was increased during the S-phase of the cell cycle in Ehrlich ascites cells. Okmura-Noji and co-workers (1990) found that glial maturation factor increased the activity of CaM kinase III in glioblasts and glioblastoma cells as they entered the S-phase, and that this increase was blocked by a CaM antagonist.…”

Section: Resultssupporting

confidence: 89%

Activity and regulation by growth factors of calmodulin-dependent protein kinase III (elongation factor 2-kinase) in human breast cancer

et al. 1998

View full text Add to dashboard Cite

Summary Calmodulin-dependent protein kinase III (CaM kinase III, elongation factor-2 kinase) is a unique member of the Ca 2+ /CaMdependent protein kinase family. Activation of CaM kinase III leads to the selective phosphorylation of elongation factor 2 (eEF-2) and transient inhibition of protein synthesis. Recent cloning and sequencing of CaM kinase III revealed that this enzyme represents a new superfamily of protein kinases. The activity of CaM kinase III is selectively activated in proliferating cells; inhibition of the kinase blocked cells in G 0 /G 1 -S and decreased viability. To determine the significance of CaM kinase III in breast cancer, we measured the activity of the kinase in human breast cancer cell lines as well as in fresh surgical specimens. The specific activity of CaM kinase III in human breast cancer cell lines was equal to or greater than that seen in a variety of cell lines with similar rates of proliferation. The specific activity of CaM kinase III was markedly increased in human breast tumour specimens compared with that of normal adjacent breast tissue. The activity of this enzyme was regulated by breast cancer mitogens. In serum-deprived MDA-MB-231 cells, the combination of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) stimulated cell proliferation and activated CaM kinase III to activities observed in the presence of 10% serum. Inhibition of enzyme activity blocked cell proliferation induced by growth factors. In MCF-7 cells separated by fluorescence-activated cell sorting, CaM kinase III was increased in S-phase over that of other phases of the cell cycle. In summary, the activity of Ca 2+ /CaM-dependent protein kinase III is controlled by breast cancer mitogens and appears to be constitutively activated in human breast cancer. These results suggest that CaM kinase III may contribute an important link between growth factor/receptor interactions, protein synthesis and the induction of cellular proliferation in human breast cancer.

show abstract

Section: Resultssupporting

confidence: 89%

Activity and regulation by growth factors of calmodulin-dependent protein kinase III (elongation factor 2-kinase) in human breast cancer

et al. 1998

View full text Add to dashboard Cite

show abstract

“…eEF2K prevents binding of eEF to the ribosome via phosphorylation of eEF and thus prevents further translation (15). The activity of eEF2K is selectively increased in proliferating cells, whereas the inhibition of the kinase remained the cells in G 0 /G 1 -S and decreased viability (7,10).…”

mentioning

confidence: 99%

Eukaryotic elongation factor 2 kinase regulates the development of hypertension through oxidative stress-dependent vascular inflammation

Usui

Okada

Hara

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Eukaryotic elongation factor 2 kinase (eEF2K) is a Ca2+/calmodulin-dependent protein kinase. We recently demonstrated that eEF2K protein increases in mesenteric artery from spontaneously hypertensive rats (SHR). Pathogenesis of hypertension is regulated in part by vascular inflammation. We tested the hypothesis whether eEF2K mediates vascular inflammatory responses and development of hypertension. In vascular endothelial cells, small interfering RNA (siRNA) against eEF2K inhibited induction of VCAM-1 and endothelial-selectin as well as monocyte adhesion by TNF-α (10 ng/ml). eEF2K siRNA inhibited phosphorylation of JNK and NF-κB p65 as well as reactive oxygen species (ROS) production by TNF-α. In vascular smooth muscle cells, eEF2K siRNA also inhibited VCAM-1 induction and phosphorylation of JNK and NF-κB by TNF-α. In vivo, increased blood pressure in SHR and ROS production, induction of inflammatory molecules, and hypertrophy in SHR superior mesenteric artery were reduced by an eEF2K inhibitor NH125 (500 μg·kg(-1)·day(-1)). In SHR superior mesenteric artery, impairment of ACh-induced relaxation was normalized by NH125. The present results for the first time demonstrate that eEF2K mediates TNF-α-induced vascular inflammation via ROS-dependent mechanism, which is at least partly responsible for the development of hypertension in SHR.

show abstract

“…The translational activity of the phosphorylated eEF-2 can be restored by the action of phosphoprotein phosphatase 2A and 2C (PP2A and PP2C, respectively) (Redpath and Proud, 1990). eEF-2 is phosphorylated by a specific eEF-2 kinase previously also known as Ca 2+ and calmodulin-dependent protein kinase III, on threonine residues (Calberg et al, 1991). Calmodulin mediates many of the intracellular effects of Ca 2+ (Park, 2001), and the eEF-2 kinase is entirely dependent on Ca 2+ /CaM for activity in mammalian tissues.…”

Section: Introductionmentioning

confidence: 99%

Effect of serum and hydrogen peroxide on the Ca2+/calmodulin-dependent phosphorylation of eukaryotic elongation factor 2(eEF-2) in Chinese hamster ovary cells

Kang

Lee²

2001

Exp Mol Med

View full text Add to dashboard Cite

Eukaryotic elongation factor eEF-2 mediates regulatory steps important for the overall regulation of mRNA translation in mammalian cells and is activated by variety of cellular conditions and factors. In this study, eEF-2 specific, Ca 2+ /CaM-dependent protein kinase III (CaM PK III), also called eEF-2 kinase, was examined under oxidative stress and cell proliferation state using CHO cells. The eEF-2 kinase activity was determined in the kinase buffer containing Ca 2+ and CaM in the presence of eEF-2 and [γ-32 P] ATP. The eEF-2 kinase activity in cell lysates was completely dependent upon Ca 2+ and CaM. Phosphorylation of eEF-2 was clearly identified in proliferating cells, but not detectable in CHO cells arrested in their growth by serum deprivation. The content of the eEF-2 protein, however, was equivalent in both cells. Using a phosphorylation statespecific antibody, we show that oxidant such as H 2 O 2 , which triggers a large influx of Ca 2+

show abstract

Increased activity of the eEF-2 specific, Ca2+ and calmodulin dependent protein kinase III during the S-phase in ehrlich ascites cells

Cited by 17 publications

References 14 publications

Activity and regulation by growth factors of calmodulin-dependent protein kinase III (elongation factor 2-kinase) in human breast cancer

Activity and regulation by growth factors of calmodulin-dependent protein kinase III (elongation factor 2-kinase) in human breast cancer

Eukaryotic elongation factor 2 kinase regulates the development of hypertension through oxidative stress-dependent vascular inflammation

Effect of serum and hydrogen peroxide on the Ca2+/calmodulin-dependent phosphorylation of eukaryotic elongation factor 2(eEF-2) in Chinese hamster ovary cells

Contact Info

Product

Resources

About