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Originally published as Genetics Published Articles Ahead of Print on July 18, 2006.
Genetics, Vol. 174, 265-270, September 2006, Copyright © 2006
doi:10.1534/genetics.106.061465
Regulation of the Drosophila melanogaster Protein, Enhancer of Rudimentary, by Casein Kinase II
Mark E. Gelsthorpe*,1,
Zehui Tan*,
Anthony Phillips*,
Joel C. Eissenberg
,
Ashley Miller*,
Janell Wallace* and
Stuart I. Tsubota*,2
* Department of Biology, Saint Louis University, St. Louis, Missouri, 63103 and Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri 63104
2 Corresponding author: Department of Biological Sciences, SUNY-Brockport, 350 New Campus Dr., Brockport, NY 14420-2973.
E-mail: stsubota{at}brockport.edu
The Drosophila melanogaster gene enhancer of rudimentary, e(r), encodes a conserved protein, ER. Most ER homologs share two casein kinase II (CKII) target sites. In D. melanogaster, these sites are T18 and S24. A third CKII site, T63, has been seen only in drosophilids. The conservation of these CKII sites, particularly T18 and S24, suggests a role for these residues in the function of the protein. To test this hypothesis, these positions were mutated either to alanine as a nonphosphorylated mimic or to glutamic acid as a phosphorylated mimic. The mutations were tested individually or in double or triple combinations for their ability to rescue either a wing truncation characteristic of the genotype e(r)p1 rhd1-12 or the synthetic lethal interaction between e(r)p2 and the Notch allele Nnd-p. All of the substitutions as single mutations rescued both mutant phenotypes, arguing that individually the phosphorylation of the three residues does not affect ER activity. The double mutants T18A-S24A and T18E-S24E and the triple mutants T18A-S24A-T63A and T18E-S24E-T63E failed to rescue. Together the data support the following model for the regulation of ER by CKII. ER that is unphosphorylated at both T18A and S24 is inactive. CKII activates ER by phosphorylating either T18 or S24. Further phosphorylation to produce the doubly phosphorylated protein inactivates ER.