Perturbation of the Calmodulin System in Transformed Cells
In eukaryotic cells, calcium acts as an intracellular signal transducer primarily through its interaction with a class of calcium binding proteins, of which calmodulin (CaM) is the most highly conserved, phylogenetically ubiquitous member (for reviews, see Van Eldik et al., 1982; Van Eldik and Roberts, 1988; Cohen and Klee, 1988). CaM transduces a calcium signal into a biological response by its ability to regulate the activity of other proteins in a calcium dependent manner. Because CaM is probably the most widely distributed mediator of intracellular calcium signals, fundamental insights can be derived from an enhanced knowlege about the genetic encoding, biosynthetic assembly and regulation of CaM-modulated calcium response pathways. Regardless, in order to understand fully the roles of CaM in the eukaryotic cell and obtain insight into how CaM-modulated pathways can respond differentially to calcium signals, it is necessary to be able to describe in some detail all of the CaM pathways for at least one biological system. This has not been done yet for any biological system. Chicken embryo fibroblasts (CEF) represent one biological system for which a relatively extensive body of information has been described. Also, CEF transformed by Rous sarcoma virus exhibit a number of phenotypic alterations that are potentially mediated by CaM and CaM binding proteins, and perturbations in CaM regulation have been described for normal and transformed CEF. In a more general sense, because perturbations of CaM pathways occur in many kinds of virus-transformed cells, knowledge of how alterations in CaM expression are coupled to oncogene expression may yield insight into how CaM-regulated calcium response pathways are involved in mechanisms of oncogenic transformation.
KeywordsMyosin Light Chain Kinase Normal Rabbit Serum Chicken Embryo Fibroblast Rous Sarcoma Virus Deoxyglucose Uptake
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- Burgess, W.H., Schleicher, M., Van Eldik, L.J., and Watterson, D.M., 1983, Comparative studies of calmodulin, in: “Calcium and Cell Function,” W.Y. Cheung, ed., Academic Press, N.Y., p. 209.Google Scholar
- Cherrington, A.D., and Vranic., M., 1986, in: “Hormonal Regulation of Gluconeogenesis,” N. Kraus and Friedmann, eds., CRC Press, FL.Google Scholar
- Cohen, P., and Klee, C.B., eds., 1988, “Molecular Aspects of Cellular Regulation -Calmodulin,” Elsevier, Amsterdam, Vol. 5.Google Scholar
- Davis, L.G., Dibner, M.D., and Battey, J.F., 1986a, “Basic Methods in Molecular Biology,” Elsevier, N.Y.Google Scholar
- Leof, E.B., Proper, J.A., Gaustin, A.S., Shipley, G.D., DiCorlto, P.E., and Moses, H.L., 1986, Induction of c-sis mRNA and activity similar to platelet-derived growth factor by transforming growth factor ß: a proposed model for indirect mitogenesis involving autocrine activity. Proc. Natl. Acad. Sci. USA. 83:2453.PubMedCrossRefGoogle Scholar
- Lukas, T.J., Haiech, J., Lau, W., Craig, T.A., Zimmer, W.E., Shattuck, R.L., Shoemaker, M.O., and Watterson, D.M., 1988, Calmodulin and calmodulin-regulated protein kinases as transducers of intracellular calcium signals. Cold Spring Harbor Symposia on Quantitative Biology, Vol. 53, p. 185.PubMedCrossRefGoogle Scholar
- Simmen, R.C.M., Tanaka, T., Ts’ui, K.F., Putkey, J.A., Scott, M.J., Lai, E.C., and Means, A.R., 1987, The structural organization of the chicken calmodulin gene: a correction. J. Biol Chem., 262:4928.Google Scholar
- Van Eldik, L.J., and Roberts, D.M., 1988, Calcium modulated proteins in pathophysiology, in: “Calcium Binding Proteins,” M.P. Thompson, ed., CRC Press, Boca Raton, FL, Vol. II, p.59.Google Scholar