Downregulation of δ CaM kinase II in human tumor cells

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Over two dozen alternative splice variants of CaMK-II, the type II Ca2+/CaM-dependent protein kinase, are encoded from four genes (α, β, γ and δ) in mammalian cells. Isozymes of α and β 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 δ CaMK-II (δ2 or δ(C)) isozyme in rodent fibroblasts. β and γ CaMK-II isozymes are minor and α CaMK-II was not expressed. The primary δ CaMK-II in human fibroblasts and the MCF10A mammary epithelial cell line was the 52 kDa δ4 CaMK-II, an isozyme identical to δ2 except for a missing 21-amino-acid C-terminal tail. δ 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 δ CaMK-II. Endogenous δ CaMK-II has a perinuclear distribution in fibroblasts and extends along neurites in PC-12 cells. These findings point to a role for δ CaMK-II isozymes in cellular differentiation.




Tombes, R. M., Mikkelsen, R. B., Jarvis, W. D., & Grant, S. (1999). Downregulation of δ CaM kinase II in human tumor cells. Biochimica et Biophysica Acta - Molecular Cell Research, 1452(1), 1–11.

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