title: Cks confers specificity to phosphorylation-dependent CDK signaling pathways.
abstract: Cks is an evolutionarily conserved protein that regulates cyclin-dependent kinase (CDK) activity. Clarifying the underlying mechanisms and cellular contexts of Cks function is critical because Cks is essential for proper cell growth, and its overexpression has been linked to cancer. We observe that budding-yeast Cks associates with select phosphorylated sequences in cell cycle-regulatory proteins. We characterize the molecular interactions responsible for this specificity and demonstrate that Cks enhances CDK activity in response to specific priming phosphosites. Identification of the binding consensus sequence allows us to identify putative Cks-directed CDK substrates and binding partners. We characterize new Cks-binding sites in the mitotic regulator Wee1 and discover a new role for Cks in regulating CDK activity at mitotic entry. Together, our results portray Cks as a multifunctional phosphoadaptor that serves as a specificity factor for CDK activity.
authors.affiliation: 1] Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, California, USA. [2].
authors.forename: Denise A
authors.initials: DA
authors.lastname: McGrath
authors.forename: Eva Rose M
authors.initials: ER
authors.lastname: Balog
authors.forename: Mardo
authors.initials: M
authors.lastname: Kõivomägi
authors.forename: Rafael
authors.initials: R
authors.lastname: Lucena
authors.forename: Michelle V
authors.initials: MV
authors.lastname: Mai
authors.forename: Alexander
authors.initials: A
authors.lastname: Hirschi
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Kellogg
authors.forename: Mart
authors.initials: M
authors.lastname: Loog
authors.forename: Seth M
authors.initials: SM
authors.lastname: Rubin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D007700:Kinetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C066503:CDC6 protein, S cerevisiae; C081185:CKS1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; C099685:SWE1 protein, S cerevisiae; D011505:Protein-Tyrosine Kinases