cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
cdc25 controls the activity of the cyclin-p34cdc2 complex by regulating the state of tyrosine phosphorylation of p34cdc2. Drosophila cdc25 protein from two different expression systems activates inactive cyclin-p34cdc2 and induces M phase in Xenopus oocytes and egg extracts. We find that the cdc25 sequence shows weak but significant homology to a phylogenetically diverse group of protein tyrosine phosphatases. cdc25 itself is a very specific protein tyrosine phosphatase. Bacterially expressed cdc25 directly dephosphorylates bacterially expressed p34cdc2 on Tyr-15 in a minimal system devoid of eukaryotic cell components, but does not dephosphorylate other tyrosine-phosphorylated proteins at appreciable rates. In addition, mutations in the putative catalytic site abolish the in vivo activity of cdc25 and its phosphatase activity in vitro. Therefore, cdc25 is a specific protein phosphatase that dephosphorylates tyrosine and possibly threonine residues on p34cdc2 and regulates MPF activation.
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
J
J
Gautier
M J
MJ
Solomon
R N
RN
Booher
J F
JF
Bazan
M W
MW
Kirschner
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D004330:Drosophila / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D009865:Oocytes / Q000502:physiology; D010446:Peptide Fragments / Q000302:isolation & purification; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity; D014158:Transcription, Genetic; D014981:Xenopus; D020666:ras-GRF1
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D012333:RNA, Messenger; D020666:ras-GRF1; D016203:CDC2 Protein Kinase; D017027:Protein Tyrosine Phosphatases