title: Transgenic inhibitors identify two roles for protein kinase A in Drosophila development.
abstract: We have initiated an analysis of protein kinase A (PKA) in Drosophila using transgenic techniques to modulate PKA activity in specific tissues during development. We have constructed GAL4/UAS-regulated transgenes in active and mutant forms that encode PKAc, the catalytic subunit of PKA, and PKI(1-31), a competitive inhibitor of PKAc. We present evidence that the wild-type transgenes are active and summarize the phenotypes produced by a number of GAL4 enhancer-detector strains. We compare the effects of transgenes encoding PKI(1-31) with those encoding PKAr*, a mutant regulatory subunit that constitutively inhibits PKAc because of its inability to bind cyclic AMP. Both inhibitors block larval growth, but only PKAr* alters pattern formation by activating the Hedgehog signaling pathway. Therefore, transgenic PKI(1-31) should provide a tool to investigate the role of PKAc in larval growth regulation without concomitant changes in pattern formation. The different effects of PKI(1-31) and PKAr* suggest two distinct roles, cytoplasmic and nuclear, for PKAc in Hedgehog signal transduction. Alternatively, PKAr* may target proteins other than PKAc, suggesting a role for free PKAr in signal transduction, a role inhibited by PKAc in reversal of the classical relationship of these subunits.
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: J L
authors.initials: JL
authors.lastname: Eklund
authors.forename: S H
authors.initials: SH
authors.lastname: Younger
authors.forename: C J
authors.initials: CJ
authors.lastname: O'Kane
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D003433:Crosses, Genetic; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D005260:Female; D005838:Genotype; D053823:Hedgehog Proteins; D019476:Insect Proteins / Q000235:genetics; D008297:Male; D008858:Microscopy, Phase-Contrast; D008957:Models, Genetic; D011770:Pyruvate Kinase / Q000502:physiology; D019076:Transgenes; D014921:Wings, Animal / Q000033:anatomy & histology
chemical_list: D001426:Bacterial Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; C077245:hh protein, Drosophila; D000242:Cyclic AMP; D011770:Pyruvate Kinase; D017868:Cyclic AMP-Dependent Protein Kinases