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Identification of Clb2 residues required for Swe1 regulation of Clb2-Cdc28 in Saccharomyces cerevisiae.

Wee1 kinases regulate the cell cycle through inhibitory phosphorylation of cyclin-dependent kinases (CDKs). Eukaryotic cells express multiple CDKs, each having a kinase subunit (Cdk) and a regulatory "cyclin" subunit that function at different stages of the cell cycle to regulate distinct processes. The cyclin imparts specificity to CDK-substrate interactions and also determines whether a particular CDK is subject to Wee1 regulation. Saccharomyces Wee1 (Swe1) inhibits Cdc28 (Cdk1) associated with the mitotic cyclin, Clb2, but not with the G(1) (Cln1, -2, and -3) or the S-phase (Clb5 and -6) cyclins. Here, we show that this specificity depends on two amino acids associated with a conserved "hydrophobic patch" (HP) motif on the cyclin surface, which mediates specificity of CDK-substrate interactions. Mutation of Clb2 residues N260 and K270 largely abrogates Clb2-Cdc28 regulation by Swe1, and reciprocal mutation of the corresponding residues in Clb5 can subject Clb5-Cdc28 to regulation by Swe1. Swe1 phosphorylation by Clb2-Cdc28, which is thought to activate Swe1 kinase, depends on N260 and K270, suggesting that specific regulation of Clb2-Cdc28 by Swe1 derives from the specific ability of Clb2 to target Swe1 for activating phosphorylation. The stable association of Swe1 with Clb2-Cdc28 also depends on these residues, suggesting that Swe1 may competitively inhibit Clb2-Cdc28 interactions with substrates, in addition to its well-known function as a regulator of CDK activity through tyrosine phosphorylation.

Pubmed ID: 18558651

Authors

  • Hu F
  • Gan Y
  • Aparicio OM

Journal

Genetics

Publication Data

June 18, 2008

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM-65494

Mesh Terms

  • Amino Acid Sequence
  • CDC28 Protein Kinase, S cerevisiae
  • Cell Cycle
  • Cell Cycle Proteins
  • Cyclin B
  • Genes, Fungal
  • Hydrophobic and Hydrophilic Interactions
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Phosphorylation
  • Protein Subunits
  • Protein-Tyrosine Kinases
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Tyrosine