Phosphorylation of Aspergillus fumigatus PkaR impacts growth and cell wall integrity through novel mechanisms

FEBS Lett. 2017 Nov;591(22):3730-3744. doi: 10.1002/1873-3468.12886. Epub 2017 Nov 9.


Protein kinase A (PKA) signaling is essential for growth and virulence of the fungal pathogen Aspergillus fumigatus. Little is known concerning the regulation of this pathway in filamentous fungi. Employing liquid chromatography-tandem mass spectroscopy, we identified novel phosphorylation sites on the regulatory subunit PkaR, distinct from those previously identified in mammals and yeasts, and demonstrated the importance of two phosphorylation clusters for hyphal growth and cell wall-stress response. We also identified key differences in the regulation of PKA subcellular localization in A. fumigatus compared with other species. This is the first analysis of the phosphoregulation of a PKA regulatory subunit in a filamentous fungus and uncovers critical mechanistic differences between PKA regulation in filamentous fungi compared with mammals and yeast species, suggesting divergent targeting opportunities.

Keywords: Aspergillus fumigatus; cell wall integrity; echinocandin; phosphorylation; protein kinase A; signaling pathway regulation.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aspergillus fumigatus / enzymology
  • Aspergillus fumigatus / genetics
  • Aspergillus fumigatus / growth & development*
  • Binding Sites
  • Cell Wall / metabolism
  • Chromatography, Liquid
  • Cyclic AMP-Dependent Protein Kinases / chemistry*
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal
  • Models, Molecular
  • Mutation
  • Phosphorylation
  • Tandem Mass Spectrometry


  • Fungal Proteins
  • Cyclic AMP-Dependent Protein Kinases