cdc2 phosphorylation is required for its interaction with cyclin.
Activation of the cdc2 protein kinase at different stages of the cell cycle is regulated by post-translational modifications and interactions with cyclins. We show that in vitro translated human cdc2 binds very poorly to A and B cyclins, unless it has been preincubated with a Xenopus egg extract. This results in the phosphorylation of cdc2 which allows binding to cyclins. The replacement of Thr161, a residue conserved and phosphorylated in other protein kinases, with valine inhibits cdc2 association with A and B cyclins. In addition, mutations in the amino-terminus of cdc2 and within the conserved 'PSTAIR' region strongly inhibit binding. The Thr161Val mutation causes a lethal phenotype in the fission yeast Schizosaccharomyces pombe, while replacement of Thr161 with glutamic acid, potentially mimicking phosphorylation, causes uncoordination of mitosis and multiple cytokinesis. These results suggest that a threonine phosphorylation/dephosphorylation cycle is involved in regulating cdc2 function.
Ducommun
B
B
Differentiation Program, European Molecular Biology Laboratory, Heidelberg, FRG.
Brambilla
P
P
Félix
M A
MA
Franza
B R
BR
Karsenti
E
E
Draetta
G
G
D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D005800:Genes, Fungal; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012568:Schizosaccharomyces / Q000235:genetics; D013912:Threonine / Q000235:genetics; D014158:Transcription, Genetic; D014981:Xenopus
D016213:Cyclins; D013912:Threonine; D016203:CDC2 Protein Kinase