Weel kinase

McGowan, C. H., and Russell, P. (1993). Human weel kinase inhibits cell division by phosphorylating p34cdc2 exclusively on tyrl5. EMBO J. 12 75-85. 

Phosphorylation at Thrl4 and TyrlS leads to inactivation of the CDKs. In the fission yeast, the weel kinase is responsible for this phosphorylation and in mammals, there are enzymes homologous to wee-1 kinase. It is not clear whether this kinase performs both phosphorylations. Phosphorylation at Thrl4 and TyrlS is of particular importance for regulation of CDK activity in mitosis. The CDC2-cychn B complex is maintained in an inactive state imtil the end of G2 phase by the phosphorylation of Thrl4 and TyrlS. At the G2/M transition, the inactive state is ended by the action of CDC2S phosphatase, which cleaves off the inhibitory phosphate residues. 

Fig. 10.14. Stability diagram established as a function of the maximum rates of cdc25 phosphatase (V i) and weel kinase (1 2). in the minimal cascade model of Fig. 10.4. TTie domain of oscillations is determined as in fig. 10.8 parameter values are as in fig. 10.6. In these conditions, a sharp threshold exists both in the first and second cycles of the cascade (see curves a in fig. 10.5a and b). The dashed line indicates the locus of the threshold value of which is equal...

Coleman, T. R., Tang, Z., and Dunphy, W. G. (1993). Negative regulation of the weel protein kinase by direct action of the niml/cdrl mitotic inducer. Cell 72 919-929. 

Rowley, R., Hudson, J., and Young, P. G. (1992). The weel protein kinase is required for radiation-induced mitotic delay. Nature 356 353-355. 

Russell, P., and Nurse, P. (1987a). Negative regulation of mitosis by weel+, a gene encoding a protein kinase homolog. Cell 49 559-567. 

Mailer There are some stories coming out that Weel comes up in meiosis II. There might be low HI kinase activity, but there is still cyclin B present in a tyrosine-phosphorylated Cdc2 complex, and this might or might not be able to signal something about cell cycle phase. 

Recent experimental studies have uncovered a direct link between the cell cycle and circadian rhythms. Thus, the circadian clock protein BMALl induces the expression of the gene Weel, which codes for the protein kinase that inactivates through phosphorylation the kinase cdkl that controls the G2/M transition [149]. This link allows the coupling of cell division to the circadian clock and explains how the latter may entrain the cell cycle clock in a variety of cell types. 

To determine the effect of circadian rhythms on anticancer drug administration, it is important to incorporate the link between the circadian clock and the cell cycle. Entrainment by the circadian clock can be included in the automaton model by considering that the protein Weel undergoes circadian variation, because the circadian clock proteins CLOCK and BMAL1 induce the expression of the Weel gene (see Fig. 10.1b) [3-5]. Weel is a kinase that phosphorylates and thereby inactivates the protein kinase cdc2 (also known as the cyclin-dependent kinase Cdkl) that controls the transition G2/M and, consequently, the onset of mitosis. 

Eattaey A, Booher RN. Mytl a Weel-type kinase that phos-phorylates Cdc2 on residue Thrl4. Prog. Cell Cycle Res. 87. 1997 3 233-240. 

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