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Lookup NU author(s): Emeritus Professor Michael Whitaker
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The p34(cdc2) protein kinase, a universal regulator of mitosis, is controlled positively and negatively by phosphorylation, and by association with B-type mitotic cyclins. In addition, activation and inactivation of p34(cdc2) are induced by Ca2+ and prevented by Ca2+ chelators in permeabilized cells and cell-free systems. This suggests that intracellular Ca2+ transients may play an important physiological role in the control of p34(cdc2) kinase activity. We have found that activators of protein kinase C can be used to block cell cycle-related alterations in intracellular Ca2+ concentration ([Ca2+](i)) in early sea urchin embryos without altering the normal resting level of Ca2+. We have used this finding to investigate whether [Ca2+](i) transients control p34(cdc2) kinase activity in living cells via a mechanism that involves cyclin B or the phosphorylation state of p34(cdc2). In the present study we show that the elimination of [Ca2+](i) transients during interphase blocks p34(cdc2) activation and entry into mitosis, while the elimination of mitotic [Ca2+](i) transients prevents p34(cdc2) inactivation and exit from mitosis. Moreover, we find that [Ca2+](i) transients are not required for the synthesis of cyclin B, its binding to p34(cdc2) or its destruction during anaphase. However, in the absence of interphase [Ca2+](i) transients p34(cdc2) does not undergo the tyrosine dephosphorylation that is required for activation, and in the absence of mitotic [Ca2+](i) transients p34(cdc2) does not undergo threonine dephosphorylation that is normally associated with inactivation. These results provide evidence that intracellular [Ca2+](i) transients trigger the dephosphorylation of p34(cdc2) at key regulatory sites, thereby controlling the timing of mitosis entry and exit.
Author(s): Suprynowicz FA, Groigno L, Whitaker M, Miller FJ, Sluder G, Sturrock J, Whalley T
Publication type: Article
Publication status: Published
Journal: Biochemical Journal
Year: 2000
Volume: 349
Issue: 2
Pages: 489-499
ISSN (print): 0264-6021
ISSN (electronic): 1470-8728
Publisher: Portland Press
URL: http://dx.doi.org/10.1042/0264-6021:3490489
DOI: 10.1042/0264-6021:3490489
PubMed id: 10880348
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