cdc25 is one of the MPM-2 antigens involved in the activation of maturation-promoting factor.
MPM-2 antigens, a discrete set of phosphoproteins that contain similar phosphoepitopes recognized by the monoclonal antibody MPM-2, are phosphorylated during M-phase induction. Our previous studies suggested that certain MPM-2 antigens are involved in the appearance of maturation-promoting factor (MPF) activity. Because the central mitotic regulator cdc2 kinase has been shown to exhibit MPF activity, we explored the possibility that certain MPM-2 antigens are regulators of cdc2 kinase. We found that MPM-2 binding of its antigens would inhibit the autoamplification of cdc2 kinase in Xenopus oocytes and interfere with cyclin-activation of cdc2 kinase in Xenopus interphase egg extract. Immunodepletion of MPM-2 antigens from cyclin-induced M-phase egg extract caused the inactivation of cdc2 kinase, which was accompanied by an inhibitory phosphorylation of p34cdc2 on Thr 14 and Tyr 15, indicating that at least one MPM-2 antigen is a positive regulator of p34cdc2 dephosphorylation. We then showed that cdc25 from M-phase arrested egg extract is an MPM-2 antigen. These results suggest that phosphorylation of the epitope recognized by MPM-2 may be a crucial event in the activation of cdc25 and that the kinase(s) that phosphorylates this MPM-2 epitope may be an important regulator of cdc2 kinase activation.
Department of Clinical Investigation, University of Texas M.D. Anderson Cancer Center, Houston 77030.
J
J
Kuang
C L
CL
Ashorn
M
M
Gonzalez-Kuyvenhoven
J E
JE
Penkala
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004789:Enzyme Activation; D016200:Maturation-Promoting Factor / Q000378:metabolism*; D008938:Mitosis; D009865:Oocytes / Q000201:enzymology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D014981:Xenopus; D020687:cdc25 Phosphatases
D000941:Antigens; D016213:Cyclins; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor; D010749:Phosphoprotein Phosphatases; D020687:cdc25 Phosphatases