Evolution of Ime2 phosphorylation sites on Cdk1 substrates provides a mechanism to limit the effects of the phosphatase Cdc14 in meiosis.
Progression through meiosis in yeast is governed by the cyclin-dependent kinase Cdk1, in concert with a related kinase called Ime2. It remains unclear how these kinases collaborate to meet the unique demands of meiotic progression. We demonstrate that Ime2 and Cdk1 phosphorylate an overlapping substrate set and that the two kinases overlap functionally as inhibitors of the ubiquitin ligase APC(Cdh1) and replication origin licensing. Surprisingly, Ime2 phosphorylates Cdk1 substrates at distinct phosphorylation sites that are highly resistant to dephosphorylation by the phosphatase Cdc14. We propose that Ime2-dependent phosphorylation of a subset of cell-cycle proteins limits the effects of Cdc14 in meiosis.
Holt
Liam J
LJ
Department of Physiology, University of California-San Francisco, San Francisco, CA 94158, USA.
Hutti
Jessica E
JE
Cantley
Lewis C
LC
Morgan
David O
DO
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D016384:Consensus Sequence; D004261:DNA Replication; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008540:Meiosis; D008954:Models, Biological; D008969:Molecular Sequence Data; D010710:Phosphates / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010710:Phosphates; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C064979:IME2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases; C069199:MCM2 protein, S cerevisiae