title: A role for CKII phosphorylation of the cactus PEST domain in dorsoventral patterning of the Drosophila embryo.
abstract: Regulated proteolysis of Cactus, the cytoplasmic inhibitor of the Rel-related transcription factor Dorsal, is an essential step in patterning of the Drosophila embryo. Signal-induced Cactus degradation frees Dorsal for nuclear translocation on the ventral and lateral sides of the embryo, establishing zones of gene expression along the dorsoventral axis. Cactus stability is regulated by amino-terminal serine residues necessary for signal responsiveness, as well as by a carboxy-terminal PEST domain. We have identified Drosophila casein kinase II (CKII) as a Cactus kinase and shown that CKII specifically phosphorylates a set of serine residues within the Cactus PEST domain. These serines are phosphorylated in vivo and are required for wild-type Cactus activity. Conversion of these serines to alanine or glutamic acid residues differentially affects the levels and activity of Cactus in embryos, but does not inhibit the binding of Cactus to Dorsal. Taken together, these data indicate that wild-type axis formation requires CKII-catalyzed phosphorylation of the Cactus PEST domain.
authors.affiliation: Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9148, USA.
authors.forename: Z P
authors.initials: ZP
authors.lastname: Liu
authors.forename: R L
authors.initials: RL
authors.lastname: Galindo
authors.forename: S A
authors.initials: SA
authors.lastname: Wasserman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019521:Body Patterning; D047390:Casein Kinase II; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018698:Glutamic Acid; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; C062236:dl protein, Drosophila; C077938:cact protein, Drosophila; D018698:Glutamic Acid; D012694:Serine; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases