title: Functional dissection of Timekeeper (Tik) implicates opposite roles for CK2 and PP2A during Drosophila neurogenesis.
abstract: Repression by E(spl)M8 during inhibitory Notch (N) signaling (lateral inhibition) is regulated, in part, by protein kinase CK2, but the involvement of a phosphatase has been unclear. The studies we report here employ Tik, a unique dominant-negative (DN) mutation in the catalytic subunit of CK2, in a Gal4-UAS based assay for impaired lateral inhibition. Specifically, overexpression of Tik elicits ectopic bristles in N(+) flies and suppresses the retinal defects of the gain-of-function allele N(spl). Functional dissection of the two substitutions in Tik (M(161)K and E(165)D), suggests that both mutations contribute to its DN effects. While the former replacement compromises CK2 activity by impairing ATP-binding, the latter affects a conserved motif implicated in binding the phosphatase PP2A. Accordingly, overexpression of microtubule star (mts), the PP2A catalytic subunit closely mimics the phenotypic effects of loss of CK2 functions in N(+) or N(spl) flies, and elicits notched wings, a characteristic of N mutations. Our findings suggest antagonistic roles for CK2 and PP2A during inhibitory N signaling.
authors.affiliation: Department of Biology, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Kunttas-Tatli
authors.forename: Anasua
authors.initials: A
authors.lastname: Bose
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Kahali
authors.forename: Clifton P
authors.initials: CP
authors.lastname: Bishop
authors.forename: Ashok P
authors.initials: AP
authors.lastname: Bidwai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D047390:Casein Kinase II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055495:Neurogenesis; D017434:Protein Structure, Tertiary; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C529534:mts protein, Drosophila; D047390:Casein Kinase II