Evolution of inhibitory serine/threonine residues as a regulatory mechanism in Hox proteins. C. Hsia , W. McGinnis. UCSD, La Jolla, CA.

   Hox genes are evolutionarily conserved transcription factors that pattern the body along the anterior-posterior axis in metazoans. Hexapods, for example, have limbs in the thoracic but not in the abdominal trunk segments while crustaceans have limbs all along the trunk. Interestingly, ectopic expression of the Drosophila melanogaster (hexapod) Hox protein Ultrabithorax (Ubx) represses limb development while ectopic expression of the Artemia franciscana (crustacean) Ubx homolog in Drosophila does not. The ability of the Ubx homologs to repress formation of Keilin's organs (embryonic limbs) and the limb-promoting gene, Distal-less (Dll) inversely correlates with their ability to be phosphorylated in vitro in the C-terminal domain by the serine/threonine (S/T) kinase casein kinase II (CKII). Drosophila Ubx (DUbx) lacks S/T residues in the C-terminal tail and is not phosphorylated in vitro by CKII. Artemia Ubx (AUbx) contains multiple S/T residues in the C-terminal tail and is phosphorylated in vitro by CKII. This suggests that inhibitory S/T phosphorylation sites in the C-terminus have evolved to regulate Ubx protein function. A closely related Hox protein, Antennapedia has been shown to require phosphorylation of S/T residues by CKII to prevent inappropriate functions such as repression of Dll transcription and Keilin's organ formation.
   We want to test if S/T phosphorylation is a general mechanism regulating Hox protein function. Abdominal-A (Abd-A) is a Hox protein expressed in non-limb forming trunk segments and capable of repressing limb-formation in Drosophila but expressed in limb-forming trunk segments in Artemia. We tested Drosophila AbdA and Artemia AbdA to see if they have differing functional abilities to repress limbs, which is associated with inhibitory S/T residues in CKII sites.