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PMID: 9843572 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The protein kinase Cdr2, related to Nim1/Cdr1 mitotic inducer, regulates the onset of mitosis in fission yeast.

Molecular biology of the cell ·Vol. 9 ·No. 12 ·1998-12-00 ·Pages 3321-34

Kanoh J, Russell P

Abstract

Cdc2-Cyclin B, the protein kinase that catalyzes the onset of mitosis, is subject to multiple forms of regulation. In the fission yeast Schizosaccharomyces pombe and most other species, a key mode of Cdc2-Cyclin B regulation is the inhibitory phosphorylation of Cdc2 on tyrosine-15. This phosphorylation is catalyzed by the protein kinases Wee1 and Mik1 and removed by the phosphatase Cdc25. These proteins are also regulated, a notable example being the inhibition of Wee1 by the protein kinase Nim1/Cdr1. The temperature-sensitive mutation cdc25-22 is synthetic lethal with nim1/cdr1 mutations, suggesting that a synthetic lethal genetic screen could be used to identify novel mitotic regulators. Here we describe that such a screen has identified cdr2(+), a gene that has an important role in the mitotic control. Cdr2 is a 775 amino acid protein kinase that is closely related to Nim1 and mitotic control proteins in budding yeast. Deletion of cdr2 causes a G2-M delay that is more severe than that caused by nim1/cdr1 mutations. Genetic studies are consistent with a model in which Cdr2 negatively regulates Wee1. This model is supported by experiments showing that Cdr2 associates with the N-terminal regulatory domain of Wee1 in cell lysates and phosphorylates Wee1 in vitro. Thus, Cdr2 is a novel mitotic control protein that appears to regulate Wee1.

MeSH Terms
ATP-Binding Cassette Transporters/genetics,metabolism Amino Acid Sequence Base Sequence CDC2 Protein Kinase/metabolism Cell Cycle Proteins Chromosome Mapping Cyclin B/metabolism DNA Primers/genetics Fungal Proteins Gene Deletion Genes, Fungal Mitosis/physiology Molecular Sequence Data Mutation Nitrogen/metabolism Nuclear Proteins Phosphorylation Protein Serine-Threonine Kinases/genetics,metabolism Protein-Tyrosine Kinases/genetics,metabolism Schizosaccharomyces/cytology,genetics,metabolism Schizosaccharomyces pombe Proteins Sequence Homology, Amino Acid Tyrosine/metabolism
Chemicals
ATP-Binding Cassette Transporters Cell Cycle Proteins Cyclin B DNA Primers Fungal Proteins Nuclear Proteins Schizosaccharomyces pombe Proteins Tyrosine cdr1 protein, S pombe wee1 protein, S pombe Protein-Tyrosine Kinases Protein Serine-Threonine Kinases CDC2 Protein Kinase Nitrogen
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kanoh J
Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Russell P
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.9.12.3321
Published
1998-12-00
Pages
3321-34
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC25629
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.9.12.3321 PMC Full Text View journal details
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