Spatial Organization in Protein Kinase A Signaling Emerged at the Base of Animal Evolution
| Autor: | Peng, Mao, Aye, Thin Thin, Snel, Berend, Van Breukelen, Bas, Scholten, Arjen, Heck, Albert J R, Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub Bioinformatics, Sub Biomol.Mass Spect. and Proteomics, UIPS - Utrecht Institute for Pharmaceutical Sciences, Theoretical Biology and Bioinformatics |
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| Rok vydání: | 2015 |
| Předmět: |
RIIa
Chemistry(all) In silico Molecular Sequence Data Computational biology Biology Proteomics Biochemistry 03 medical and health sciences AKAP proteomics 0302 clinical medicine Catalytic Domain evolution Taverne Animals PKA Amino Acid Sequence Protein kinase A signaling Evolutionary dynamics Protein kinase A Conserved Sequence Phylogeny 030304 developmental biology 0303 health sciences Sequence Homology Amino Acid Kinase General Chemistry Biological Evolution Cyclic AMP-Dependent Protein Kinases Cell biology Multicellular organism Docking (molecular) 030217 neurology & neurosurgery Signal Transduction Subcellular Fractions |
| Zdroj: | Journal of Proteome Research, 14(7), 2976. American Chemical Society |
| ISSN: | 1535-3907 1535-3893 |
| DOI: | 10.1021/acs.jproteome.5b00370 |
| Popis: | In phosphorylation-directed signaling, spatial and temporal control is organized by complex interaction networks that diligently direct kinases toward distinct substrates to fine-tune specificity. How these protein networks originate and evolve into complex regulatory machineries are among the most fascinating research questions in biology. Here, spatiotemporal signaling is investigated by tracing the evolutionary dynamics of each functional domain of cAMP-dependent protein kinase (PKA) and its diverse set of A-kinase anchoring proteins (AKAPs). Homologues of the catalytic (PKA-C) and regulatory (PKA-R) domains of the (PKA-R)2-(PKA-C)2 holoenzyme were found throughout evolution. Most variation was observed in the RIIa of PKA-R, crucial for dimerization and docking to AKAPs. The RIIa domain was not observed in all PKA-R homologues. In the fungi and distinct protist lineages, the RIIa domain emerges within PKA-R, but it displays large sequence variation. These organisms do not harbor homologues of AKAPs, suggesting that efficient docking to direct spatiotemporal PKA activity evolved in multicellular eukaryotes. To test this in silico hypothesis, we experimentally screened organisms with increasing complexity by cAMP-based chemical proteomics to reveal that the occurrence of PKA-AKAP interactions indeed coincided and expanded within vertebrates, suggesting a crucial role for AKAPs in the advent of metazoan multicellularity. |
| Databáze: | OpenAIRE |
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