Psychiatry related information on Pka-C3

• Drosophila melanogaster bearing mutations in the DCO gene, which encodes the major catalytic subunit of cAMP-dependent protein kinase (PKA), displays arrhythmic locomotor activity strongly suggesting a role for PKA in the circadian timing system [1].
• The findings suggest that in the mutant's nerve cells the state of phosphorylation of the regulatory subunit of cAMP-dependent protein kinase is altered, which may contribute to the biochemical disorder leading to the memory deficit [2].

High impact information on Pka-C3

• 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 [3].
• The cAMP-dependent protein kinase (PKA) has been shown to mediate the vast majority of cellular responses to the intracellular second messenger, cAMP, in eukaryotes [4].
• Two of these genes (DC1 and DC2) are sufficiently similar to DC0 in sequence (45% and 49% amino acid identity, respectively) that they could conceivably encode products of overlapping function [5].
• In a screen for such mutants in Drosophila melanogaster, we found that heterozygous mutations of DCO (DCO/+), which encodes the major catalytic subunit of cAMP-dependent protein kinase (PKA), delay AMI more than twofold without affecting lifespan or memory at early ages [6].
• Two distinct mechanisms regulate synaptic efficacy at the Drosophila neuromuscular junction (NMJ): a PKA-dependent modulation of quantal size and a retrograde regulation of presynaptic release [7].

Biological context of Pka-C3

• This editing likely reduces or abolishes synapsin phosphorylation by PKA [8].
• Overexpression of the G protein subunit Galpha(s) or of the catalytic subunit of protein kinase A (PKA) partially mimicked and enhanced the defects caused by ectopic expression of AdoR [9].
• Similar to our earlier results with Shh, we observed the induction of floor plate and motor neuron markers in embryos expressing the dominant negative PKA transgene and the loss of dorsal gene expression at rostral levels [10].
• Furthermore, transgenes expressing DC2 from a DC0 promoter did not efficiently rescue a variety of DC0 mutant phenotypes [11].
• These observations indicate that DC2 is not an essential gene and is unlikely to be functionally redundant with DC0, which has multiple unique functions during development [11].

Anatomical context of Pka-C3

• This AKAP-bound pool of PKA is acting within neurons of the mushroom bodies to support a late phase of aversive memory [12].
• While the visual neuropiles, the antennal lobes, and structures of the central brain exhibit intermediate immunostaining, the mushroom bodies show high labeling and contain a three- to fourfold higher PKA activity compared to other neuropiles [13].
• Here we report that the type 1 regulatory subunit of cAMP-dependent protein kinase (Pka-R1) is crucial for the restriction of Oskar protein to the oocyte posterior [14].
• The central nervous system isoform DTH I is activated through phosphorylation by cAMP-dependent protein kinase (PKA) in the absence of dopamine [15].
• We now report that MDR in this cell line is partially reversed by the type I cAMP-dependent protein kinase (PKA) inhibitor, 8-Cl-cAMP [16].

Associations of Pka-C3 with chemical compounds

• Dopamine, serotonin, and octopamine, however, cause an increase in PKA activity in Kenyon cells [13].
• Increased PKA activity also decreases the response to direct iontophoresis of glutamate onto postsynaptic receptors [7].
• The affinity of VASP for F-actin is controlled by phosphorylation of serine 157 by cAMP-dependent protein kinase [17].
• The latter forms a so-called cysteine/serine-rich domain with three cysteine pairs suggestive of ATP binding, as well as three potential cAMP-dependent protein kinase (PKA) recognition sites obviously phosphorylated by PKA [18].
• The effects of the activity of phosphodiesterase, adenylate cyclase, and protein phosphatase on the kinetics of cAMP-dependent protein kinase have been modeled, as have the effects of different ratios of regulatory subunit to catalytic subunit [19].

References