The utilization of different carbon sources in filamentous fungi underlies a complex regulatory network governed by signaling events of different protein kinase pathways, including
the high osmolarity glycerol (HOG) and protein kinase A (PKA) pathways. This work unraveled cross-talk events between these pathways in governing the ...
The utilization of different carbon sources in filamentous fungi underlies a complex regulatory network governed by signaling events of different protein kinase pathways, including
the high osmolarity glycerol (HOG) and protein kinase A (PKA) pathways. This work unraveled cross-talk events between these pathways in governing the utilization of preferred (glucose) and non-preferred (xylan, xylose) carbon sources in the reference fungus Aspergillus
nidulans. An initial screening of a library of 103 non-essential protein kinase (NPK) deletion
strains identified several mitogen-activated protein kinases (MAPKs) to be important for carbon catabolite repression (CCR). We selected the MAPKs Ste7, MpkB, and PbsA for further
characterization and show that they are pivotal for HOG pathway activation, PKA activity,
CCR via regulation of CreA cellular localization and protein accumulation, as well as for
hydrolytic enzyme secretion. Protein-protein interaction studies show that Ste7, MpkB, and
PbsA are part of the same protein complex that regulates CreA cellular localization in the
presence of xylan and that this complex dissociates upon the addition of glucose, thus allowing CCR to proceed. Glycogen synthase kinase (GSK) A was also identified as part of this
protein complex and shown to potentially phosphorylate two serine residues of the HOG
MAPKK PbsA. This work shows that carbon source utilization is subject to cross-talk regulation by protein kinases of different signaling pathways. Furthermore, this study provides a
model where the correct integration of PKA, HOG, and GSK signaling events are required
for the utilization of different carbon sources.
