had phenotypes in cell cycle phases that correspond 
to the peaks of PPl activity. 
These results indicate that the initiation of cdc25 
activation is regulated at least in part by changes in 
PPl activity. PPl is also regulated by the presence of 
incompletely replicated DNA, since its activity re- 
mains high when the cell cycle is arrested in S phase 
by inhibitors of DNA synthesis. It is likely there are 
additional targets besides cdc25 for regulation by 
PPl . Elucidating the mechanism by which PPl activ- 
ity oscillates merits urgent attention, as does identi- 
fication of the protein kinase (s) responsible for 
phosphorylating and activating cdc25. 
The cdk2 Protein Kinase and Meiotic 
Metaphase Arrest 
Genetic evidence in yeast indicates that the cdc2 
gene controls both the Gj and Gj restriction point. 
However, in higher eukaryotes, several genes 
closely related to cdc2 (termed cdks, for cyclin- 
dependent kinases) have been cloned by various lab- 
oratories, and a role for them in Gj/S regulation has 
been suggested. The best-studied cdk is cdk2 in 
Xenopus. The mRNA for this gene is stored in the 
oocyte and becomes translated only during the mei- 
otic cell cycles of oocyte maturation, although the 
kinase activity of cdk2 persists into the early embry- 
onic cell cycles. Xenopus cdk2 is active as a protein 
kinase only in a complex with other proteins, whose 
identity is unknown but is distinct from cyclins A 
and B. 
This year substantial progress was made in under- 
standing the role of cdk2 in the meiotic cell cycles 
of Xenopus. In meiosis II, cdk2 kinase activity rises, 
although the polypeptide accumulates earlier, in 
meiosis I. To determine if elevated cdk2 activity is 
important for meiosis, Dr. Brian Gabrielli designed 
antisense oligodeoxynucleotides against cdk2 and 
showed that injection of these into oocytes prior to 
stimulation of meiotic maturation abolished expres- 
sion of cdk2. No effect of cdk2 ablation was ob- 
served on cdc2 kinase activity in meiosis I. In meio- 
sis II, however, metaphase arrest failed to occur and 
the oocytes proceeded directly from meiosis II into 
the first embryonic cell cycle. Important control ex- 
periments showed that injection of purified cdk2 
into oocytes along with the antisense oligonucleo- 
tides restored a metaphase II arrest with elevated 
cdc2 kinase activity. It had been known for some 
time that metaphase II arrest requires the expression 
of the c-mos proto-oncogene kinase plus one or 
more newly synthesized proteins. The present re- 
sults suggest cdk2 as one of the new proteins re- 
quired along with c-mos for meiosis II metaphase 
arrest. The cooperation between the c-mos^^ and 
cdk2 protein kinases in meiosis II arrest is another 
example of the complex network linking cell 
growth control by oncogenes with cell cycle control 
elements. 
Dr. Mailer is also Professor of Pharmacology at 
the University of Colorado School of Medicine, 
Denver. 
Articles 
Gabrielli, B.G., Roy, L.M., Gautier, J., Philippe, M., 
and Mailer, J.L. 1992. A cdc2-Te\ated kinase 
oscillates in the cell cycle independently of cy- 
clins G2/M and cdc2. f Biol Chem 267:1969- 
1975. 
Izumi, T., Walker, D.H., and Mailer, J.L. 1992. 
Periodic changes in phosphorylation of the Xeno- 
pus cdc25 phosphatase regulate its activity. Mol 
Biol Cell 3:927-939. 
Lee, M.S., Ogg, S., Xu, M., Parker, L.L., Donoghue, 
D.J., Mailer, J.L., and Piwnica-Worms, H. 1992. 
cdc25^ encodes a protein phosphatase that de- 
phosphorylates p34^''^^ Mol Biol Cell 3:73-84. 
Mailer, J.L., Roy, L.M., and Izumi, T. 1991. Cell 
cycle and mitotic control in Xenopus eggs. Cold 
Spring Harb Symp Quant Biol 56:533-538. 
Walker, D.H., and Mailer, J.L. 1991. Role for cy- 
clin A in the dependence of mitosis on comple- 
tion of DNA replication. Nature 554:514-517 ■ 
Walker, D.H., DePaoli-Roach, A.A., and Mailer, 
J.L. 1992. Multiple roles for protein phosphatase 
1 in regulating the Xenopus early embryonic cell 
cycle. Mol Biol Cell 3:687-698. 
CELL BIOLOGY AND REGULATION 93 
