Cyclin activation of p34cdc2.
The gradual accumulation of cyclin in the frog egg induces an abrupt and concerted activation of p34cdc2 that initiates mitosis. Activation is delayed even after the accumulation of cyclin to a critical threshold concentration. We have reproduced these unusual kinetic properties of p34cdc2 activation in vitro using bacterially expressed cyclin proteins and extracts derived from Xenopus eggs. Abrupt activation follows a lag period, the length of which is independent of the concentration of cyclin. The threshold concentration of cyclin and the length of the lag period are regulated by INH, an inhibitor of MPF activation in oocytes recently identified as a type 2A protein phosphatase. Binding to cyclin induces both tyrosine and threonine phosphorylation of the previously unphosphorylated p34cdc2, rendering it inactivated. The concerted transition into mitosis involves both a reduction in the rate of p34cdc2 phosphorylation on tyrosine and an increase in its rate of dephosphorylation.
Solomon
M J
MJ
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Glotzer
M
M
Lee
T H
TH
Philippe
M
M
Kirschner
M W
MW
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002848:Chromatography, DEAE-Cellulose; D016213:Cyclins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004789:Enzyme Activation; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D007399:Interphase; D008938:Mitosis; D008954:Models, Biological; D009865:Oocytes / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D012617:Sea Urchins; D014981:Xenopus
D016213:Cyclins; D011993:Recombinant Fusion Proteins; D016203:CDC2 Protein Kinase