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Functional dissection of Timekeeper ( Tik ) implicates opposite roles for CK2 and PP2A during Drosophila neurogenesis
Author(s) -
KunttasTatli Ezgi,
Bose Anasua,
Kahali Bhaskar,
Bishop Clifton P.,
Bidwai Ashok P.
Publication year - 2009
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.20543
Subject(s) - neurogenesis , drosophila (subgenus) , biology , dissection (medical) , neuroscience , anatomy , genetics , gene
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. genesis 47:647–658, 2009. © 2009 Wiley‐Liss, Inc.