Functional dissection ofTimekeeper(Tik) implicates opposite roles for CK2 and PP2A duringDrosophilaneurogenesis
| Autor: | Clifton P. Bishop, Bhaskar Kahali, Ezgi Kunttas-Tatli, Ashok P. Bidwai, Anasua Bose |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular animal structures Neurogenesis Protein subunit Molecular Sequence Data Phosphatase Biology medicine.disease_cause Article Endocrinology Catalytic Domain Genetics medicine Animals Drosophila Proteins Humans Amino Acid Sequence Casein Kinase II Psychological repression Mutation Receptors Notch fungi Cell Biology Protein phosphatase 2 Molecular biology Protein Structure Tertiary Drosophila melanogaster embryonic structures Casein kinase 2 Signal transduction Sequence Alignment Signal Transduction |
| Zdroj: | genesis. 47:647-658 |
| ISSN: | 1526-968X 1526-954X |
| DOI: | 10.1002/dvg.20543 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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