Related Experiment Video
Updated: Jul 20, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Downregulation of delta CaM kinase II in human tumor cells
R M Tombes1, R B Mikkelsen, W D Jarvis
1Massey Cancer Center and Department of Biology, Medical College of Virginia Commonwealth University, Richmond, VA 23298, USA. rtombes@hsc.vcu.edu
Abstract:
Over two dozen alternative splice variants of CaMK-II, the type II Ca(2+)/CaM-dependent protein kinase, are encoded from four genes (alpha, beta, gamma and delta) in mammalian cells. Isozymes of alpha and beta CaMK-II are well characterized in brain; however, an understanding of the relative endogenous levels of CaMK-II isozymes in a wide variety of non-neuronal cells has not yet been described. In this study, we have demonstrated that CaMK-II consists primarily of the 54 kDa delta CaMK-II (delta(2) or delta(C)) isozyme in rodent fibroblasts. beta and gamma CaMK-II isozymes are minor and alpha CaMK-II was not expressed. The primary delta CaMK-II in human fibroblasts and the MCF10A mammary epithelial cell line was the 52 kDa delta(4) CaMK-II, an isozyme identical to delta(2) except for a missing 21-amino-acid C-terminal tail. delta CaMK-II levels were diminished in both human and rodent fibroblasts after SV40 transformation and in the mammary adenocarcinoma MCF7 cell line when compared to MCF10A cells. In fact, most tumor cells exhibited CaMK-II specific activities which were two- to tenfold lower than in untransformed fibroblasts. We conducted complementary CaMK-II studies on the NGF-induced differentiation of rat PC-12 cells. Although no new synthesis of CaMK-II occurs, neurite outgrowth in these cells is accompanied by a preferential activation of delta CaMK-II. Endogenous delta CaMK-II has a perinuclear distribution in fibroblasts and extends along neurites in PC-12 cells. These findings point to a role for delta CaMK-II isozymes in cellular differentiation.
Insights
This study reveals that delta CaMK-II (Ca(2+)/CaM-dependent protein kinase II) isozymes are prevalent in non-neuronal cells, with levels decreasing in transformed and tumor cells, suggesting a role in cellular differentiation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Mammalian cells express over two dozen alternative splice variants of CaMK-II (Ca(2+)/CaM-dependent protein kinase) from four genes (alpha, beta, gamma, delta).
- While alpha and beta CaMK-II isozymes are well-characterized in the brain, their relative endogenous levels in non-neuronal cells are not well described.
Purpose of the Study:
- To investigate the relative endogenous levels and distribution of CaMK-II isozymes in various non-neuronal mammalian cells.
- To explore the role of delta CaMK-II isozymes in cellular differentiation, particularly in response to NGF-induced differentiation of PC-12 cells.
Main Methods:
- Western blot analysis to detect and quantify CaMK-II isozymes in different cell lines (rodent fibroblasts, human fibroblasts, MCF10A, MCF7, PC-12).
- Measurement of CaMK-II specific activities in various cell types.
- Immunofluorescence microscopy to determine the cellular localization of endogenous delta CaMK-II.
Main Results:
- Rodent fibroblasts primarily express the 54 kDa delta CaMK-II (delta(2)/delta(C)) isozyme; alpha CaMK-II is absent, and beta/gamma are minor.
- Human fibroblasts and MCF10A cells predominantly express the 52 kDa delta(4) CaMK-II.
- Delta CaMK-II levels and activity are significantly reduced in SV40-transformed fibroblasts, MCF7 tumor cells compared to MCF10A cells.
- NGF-induced differentiation of PC-12 cells shows preferential activation of delta CaMK-II without new synthesis, with perinuclear distribution in fibroblasts and neurite extension in PC-12 cells.
Conclusions:
- Delta CaMK-II isozymes are the predominant forms in diverse non-neuronal cells.
- Reduced delta CaMK-II levels and activity are associated with cellular transformation and tumorigenesis.
- Delta CaMK-II localization and activation during differentiation suggest its involvement in cellular differentiation processes.
Related Concept Videos
Inhibition of Cdk Activity
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades
PI3K/mTOR/AKT Signaling Pathway
Inhibition of CDK Activity

