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Gene Review

Pka-C1  -  cAMP-dependent protein kinase 1

Drosophila melanogaster

Synonyms: 6353, CG4379, CdkA, Cos, Cos-1, ...
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Disease relevance of Pka-C1


Psychiatry related information on Pka-C1

  • A role for cAMP signaling in circadian processes is also suggested by an analysis of DC0 mutants, which have severe kinase deficits and display arrhythmic locomotor activity [4].

High impact information on Pka-C1


Biological context of Pka-C1

  • Here we show that the catalytic subunit of cyclic AMP-dependent protein kinase A (Pka-C1) is required for the correct spatial regulation of dpp expression during eye development [10].
  • AMI is restored when a DCO transgene is expressed in mushroom bodies, structures important for olfactory memory formation [11].
  • 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) [12].
  • However, most Drosophila NF1 mutant phenotypes, including an overall growth deficiency, are not readily modified by manipulating Ras signaling strength, but are rescued by increasing signaling through the cAMP-dependent protein kinase A pathway [13].
  • An A-kinase anchoring protein is required for protein kinase A regulatory subunit localization and morphology of actin structures during oogenesis in Drosophila [14].

Anatomical context of Pka-C1

  • Loss of Pka-C1 function is sufficient to produce an ectopic morphogenetic wave marked by premature ectopic photoreceptor differentiation and non-autonomous propagation of dpp expression [10].
  • We describe mutation affecting Protein Kinase A (PKA) that act in the germ line to disrupt both microtubule distribution and RNA localization along this axis [15].
  • We found that ectopic expression of Hedgehogs or inhibition of protein kinase A in zebrafish embryos induces slow muscle precursors throughout the somite but muscle pioneer cells only in the middle of the somite [16].
  • In this report we demonstrate, by two different methods, that reduction or elimination of protein kinase A activity had no effect on phenotypes generated by activation of Gs alpha pathways in Drosophila wing epithelial cells [17].
  • Induction of ectopic motor neurons by neurogeninl requires coexpression of a dominant negative regulatory subunit of protein kinase A, an intracellular transducer of hedgehog signals [18].

Associations of Pka-C1 with chemical compounds

  • In addition, we demonstrate that, in cell culture, the mutation of any one of the three serine-containing PKA sites abolishes the proteolytic processing of CI [19].
  • Furthermore, our studies predict the existence of feedback inhibition through protein kinase A on the InsP(3) receptor by increased levels of 20-hydroxyecdysone [20].
  • The enhancement of Slob kinase activity by PKAc pretreatment is eliminated when serine 54 in Slob is mutated to alanine (S54A) [21].

Physical interactions of Pka-C1


Regulatory relationships of Pka-C1


Other interactions of Pka-C1

  • We present a model where low signaling is initiated when a Costal inhibitory site on the Smoothened cytoplasmic tail shifts the regulatory complex to its low state [23].
  • The mutant PKAr*, defective in binding cAMP, is shown to activate Hh target genes solely through its ability to bind and inhibit endogenous PKAc [12].
  • Here we present evidence that removing activity of the gene encoding cyclic AMP-dependent protein kinase A (pka) is functionally equivalent to removing ptc activity or to providing cells with the Hh signal [26].
  • Ci is phosphorylated by GSK3 after a primed phosphorylation by protein kinase A (PKA), and mutating GSK3-phosphorylation sites in Ci blocks its processing and prevents the production of the repressor form [27].
  • The ratio of these forms, which is regulated positively by hh signaling and negatively by PKA activity, determines the on/off status of hh target gene expression [19].

Analytical, diagnostic and therapeutic context of Pka-C1


  1. Anthrax lethal factor and edema factor act on conserved targets in Drosophila. Guichard, A., Park, J.M., Cruz-Moreno, B., Karin, M., Bier, E. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Analysis of the zebrafish smoothened mutant reveals conserved and divergent functions of hedgehog activity. Chen, W., Burgess, S., Hopkins, N. Development (2001) [Pubmed]
  3. Drosophila melanogaster deficient in protein kinase A manifests behavior-specific arrhythmia but normal clock function. Majercak, J., Kalderon, D., Edery, I. Mol. Cell. Biol. (1997) [Pubmed]
  4. Altered circadian pacemaker functions and cyclic AMP rhythms in the Drosophila learning mutant dunce. Levine, J.D., Casey, C.I., Kalderon, D.D., Jackson, F.R. Neuron (1994) [Pubmed]
  5. Drosophila melanogaster neurofibromatosis-1: ROS, not Ras? Walker, J.A., Bernards, A. Nat. Genet. (2007) [Pubmed]
  6. Proteolysis of the Hedgehog signaling effector Cubitus interruptus requires phosphorylation by Glycogen Synthase Kinase 3 and Casein Kinase 1. Price, M.A., Kalderon, D. Cell (2002) [Pubmed]
  7. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Wang, B., Fallon, J.F., Beachy, P.A. Cell (2000) [Pubmed]
  8. Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development. Li, W., Ohlmeyer, J.T., Lane, M.E., Kalderon, D. Cell (1995) [Pubmed]
  9. cAMP-dependent protein kinase and hedgehog act antagonistically in regulating decapentaplegic transcription in Drosophila imaginal discs. Pan, D., Rubin, G.M. Cell (1995) [Pubmed]
  10. Regulation of furrow progression in the Drosophila eye by cAMP-dependent protein kinase A. Strutt, D.I., Wiersdorff, V., Mlodzik, M. Nature (1995) [Pubmed]
  11. The Drosophila DCO mutation suppresses age-related memory impairment without affecting lifespan. Yamazaki, D., Horiuchi, J., Nakagami, Y., Nagano, S., Tamura, T., Saitoe, M. Nat. Neurosci. (2007) [Pubmed]
  12. Genetic evidence for a protein kinase A/cubitus interruptus complex that facilitates processing of cubitus interruptus in Drosophila. Kiger, J.A., O'Shea, C. Genetics (2001) [Pubmed]
  13. Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons. Walker, J.A., Tchoudakova, A.V., McKenney, P.T., Brill, S., Wu, D., Cowley, G.S., Hariharan, I.K., Bernards, A. Genes Dev. (2006) [Pubmed]
  14. An A-kinase anchoring protein is required for protein kinase A regulatory subunit localization and morphology of actin structures during oogenesis in Drosophila. Jackson, S.M., Berg, C.A. Development (2002) [Pubmed]
  15. RNA localization along the anteroposterior axis of the Drosophila oocyte requires PKA-mediated signal transduction to direct normal microtubule organization. Lane, M.E., Kalderon, D. Genes Dev. (1994) [Pubmed]
  16. Positive and negative regulation of muscle cell identity by members of the hedgehog and TGF-beta gene families. Du, S.J., Devoto, S.H., Westerfield, M., Moon, R.T. J. Cell Biol. (1997) [Pubmed]
  17. Activation of protein kinase A-independent pathways by Gs alpha in Drosophila. Wolfgang, W.J., Roberts, I.J., Quan, F., O'Kane, C., Forte, M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  18. The activity of neurogenin1 is controlled by local cues in the zebrafish embryo. Blader, P., Fischer, N., Gradwohl, G., Guillemot, F., Strähle, U. Development (1997) [Pubmed]
  19. Mutants of cubitus interruptus that are independent of PKA regulation are independent of hedgehog signaling. Chen, Y., Cardinaux, J.R., Goodman, R.H., Smolik, S.M. Development (1999) [Pubmed]
  20. Interactions between the inositol 1,4,5-trisphosphate and cyclic AMP signaling pathways regulate larval molting in Drosophila. Venkatesh, K., Siddhartha, G., Joshi, R., Patel, S., Hasan, G. Genetics (2001) [Pubmed]
  21. The slowpoke channel binding protein Slob from Drosophila melanogaster exhibits regulatable protein kinase activity. Zeng, H., Fei, H., Levitan, I.B. Neurosci. Lett. (2004) [Pubmed]
  22. Modulation of Drosophila slowpoke calcium-dependent potassium channel activity by bound protein kinase a catalytic subunit. Zhou, Y., Wang, J., Wen, H., Kucherovsky, O., Levitan, I.B. J. Neurosci. (2002) [Pubmed]
  23. Smoothened translates Hedgehog levels into distinct responses. Hooper, J.E. Development (2003) [Pubmed]
  24. The regulatory subunit of a cGMP-regulated protein kinase A of Trypanosoma brucei. Shalaby, T., Liniger, M., Seebeck, T. Eur. J. Biochem. (2001) [Pubmed]
  25. The Rap1 GTPase functions as a regulator of morphogenesis in vivo. Asha, H., de Ruiter, N.D., Wang, M.G., Hariharan, I.K. EMBO J. (1999) [Pubmed]
  26. Signal transduction by cAMP-dependent protein kinase A in Drosophila limb patterning. Lepage, T., Cohen, S.M., Diaz-Benjumea, F.J., Parkhurst, S.M. Nature (1995) [Pubmed]
  27. Shaggy/GSK3 antagonizes Hedgehog signalling by regulating Cubitus interruptus. Jia, J., Amanai, K., Wang, G., Tang, J., Wang, B., Jiang, J. Nature (2002) [Pubmed]
  28. Preferential expression in mushroom bodies of the catalytic subunit of protein kinase A and its role in learning and memory. Skoulakis, E.M., Kalderon, D., Davis, R.L. Neuron (1993) [Pubmed]
  29. Spontaneous acetylcholine secretion from developing growth cones of Drosophila central neurons in culture: effects of cAMP-pathway mutations. Yao, W.D., Rusch, J., Poo, M., Wu, C.F. J. Neurosci. (2000) [Pubmed]
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