title: Genetic evidence for a protein kinase A/cubitus interruptus complex that facilitates processing of cubitus interruptus in Drosophila.
abstract: Hedgehog (Hh) activates a signal transduction pathway regulating Cubitus interruptus (Ci). In the absence of Hh, full-length Ci (Ci-155) is bound in a complex that includes Costal2 (Cos2) and Fused (Fu). Ci-155 is phosphorylated by protein kinase A (PKA), inducing proteolysis to Ci-75, a transcriptional repressor. Hh signaling blocks proteolysis and produces an activated Ci-155 transcriptional activator. The relationship between PKA and the Ci/Cos2/Fu complex is unclear. Here we examine Hh target gene expression caused by mutant forms of PKA regulatory (PKAr) and catalytic (PKAc) subunits and by the PKAc inhibitor PKI(1-31). The mutant PKAr*, defective in binding cAMP, is shown to activate Hh target genes solely through its ability to bind and inhibit endogenous PKAc. Surprisingly, PKAcA75, a catalytically impaired mutant, also activates Hh target genes. To account for this observation, we propose that PKAc phosphorylation targeting Ci-155 for proteolysis is regulated within a complex that includes PKAc and Ci-155 and excludes PKI(1-31). This complex may permit processive phosphorylation of Ci-155 molecules, facilitating their processing to Ci-75.
authors.affiliation: Molecular and Cellular Biology, University of California, Davis, California 95616, USA. jakiger@ucdavis.edu
authors.forename: J A
authors.initials: JA
authors.lastname: Kiger
authors.forename: C
authors.initials: C
authors.lastname: O'Shea
mesh_terms: D000483:Alleles; D000818:Animals; D002384:Catalysis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila / Q000201:enzymology / Q000378:metabolism*; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors; D019076:Transgenes
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D014157:Transcription Factors; C092937:ci protein, Drosophila; C077245:hh protein, Drosophila; D017868:Cyclic AMP-Dependent Protein Kinases