Brief summary of experimental advances

In amphibian eggs (fig. 10.2), the cell cycle has a simple form as it consists in the periodic alternation of mitosis and interphase. Mitosis is associated with the activation of a factor known as maturation (or mitosis) promoting factor (MPF). Activation of MPF is triggered by the building up to a threshold of cyclin, a protein whose name reflects its 

The interaction of cdc2 kinase with cyclin is in fact central to the mechanism of the mitotic oscillator in all eukaryotic cells (Nurse, 1990). The situation encountered in the early stages of amphibian development represents the simplest form of mitotic trigger mechanism 

Advances made over the last six years have permitted the characterization of the biochemical mechanism through which cdc2 kinase becomes activated for reviews, see Draetta (1990), Mailer (1990), King et al. (1994) emd Morgan (1995). Such a process relies primarily (fig. 10.3) on the dephosphorylation of cdc2 kinase on tyrosine (Tyr) 15 by a tyrosine phosphatase (Draetta Beach, 1989 Gautier etal., 1989  

The inhibitory effect of the phosphorylation of cdc2 kinase on TyrlS stems from the fact that this residue is located in the ATP-binding domain of the enzyme (Gould Nurse, 1989). In vertebrate cells, but apparently not in yeast, phosphorylation of threonine (Thr) 14, a second residue located in that site, also inhibits cdc2 kinase (Krek Nigg, 1991 Norbury, Blow Nurse, 1991). In fission yeast, the kinase phos- 

A conspicuous feature of cyclin and cdc2 interactions is the occurrence of sharp thresholds in the dependence of cdc2 kinase activation by cyclin, and in the dependence of cyclin degradation on active cdc2 kinase (Minshull et al, 1989 Murray Kirschner, 1989b Felix et al, 1990 Karsenti, Verde Felix, 1991 King et al, 1994). Besides the 

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