title: mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2.
abstract: wee1 acts antagonistically to cdc25 in the tyrosine dephosphorylation and activation of cdc2, yet biochemical evidence suggests that wee1 is not required for tyrosine phosphorylation and its role is obscure. We show here that a related 66 kd kinase, called mik1, acts redundantly with wee1 in the negative regulation of cdc2 in S. pombe. A null allele of mik1 has no discernible phenotype, but a mik1 wee1 double mutant is hypermitotically lethal: all normal M phase checkpoints are bypassed, including the requirement for initiation of cell cycle "start," completion of S phase, and function of the cdc25+ mitotic activator. In the absence of mik1 and wee1 activity, cdc2 rapidly loses phosphate on tyrosine, both in strains undergoing mitotic lethality and in those that are viable owing to a compensating mutation within cdc2. The data suggest that mik1 and wee1 act cooperatively on cdc2, either directly as the inhibitory tyrosine kinase or as essential activators of that kinase.
authors.affiliation: Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
authors.forename: K
authors.initials: K
authors.lastname: Lundgren
authors.forename: N
authors.initials: N
authors.lastname: Walworth
authors.forename: R
authors.initials: R
authors.lastname: Booher
authors.forename: M
authors.initials: M
authors.lastname: Dembski
authors.forename: M
authors.initials: M
authors.lastname: Kirschner
authors.forename: D
authors.initials: D
authors.lastname: Beach
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D005800:Genes, Fungal / Q000502:physiology; D008938:Mitosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D019000:Phosphotyrosine; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D019000:Phosphotyrosine; D014443:Tyrosine; D016203:CDC2 Protein Kinase