INH, a negative regulator of MPF, is a form of protein phosphatase 2A.
MPF, a protein kinase complex consisting of cyclin and p34cdc2 subunits, promotes the G2 to M phase transition in eukaryotic cells. The pathway of activation and inactivation of MPF is not well understood, although there is strong evidence that removal of phosphate from a tyrosine residue on p34cdc2 is part of the activation process. INH was originally identified as an activity that could inhibit the posttranslational activation of a latent form of MPF, called pre-MPF, in immature (G2 phase-arrested) Xenopus oocytes. We have purified INH and demonstrated that it is a form of protein phosphatase 2A. Both INH and the catalytic subunit of protein phosphatase 2A can directly inactivate an isolated p34cdc2-cyclin complex. Both cyclin and p34cdc2 become dephosphorylated; the rate of inactivation closely parallels the removal of phosphate from a specific site on p34cdc2. We propose that INH opposes MPF activation by reversing this critical phosphorylation.
Lee
T H
TH
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Solomon
M J
MJ
Mumby
M C
MC
Kirschner
M W
MW
D000818:Animals; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D006657:Histones / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000302:isolation & purification / Q000378:metabolism*; D054648:Protein Phosphatase 2; D014982:Xenopus laevis
D016213:Cyclins; D006657:Histones; D046911:Macromolecular Substances; D016203:CDC2 Protein Kinase; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2