Figure 7
From: Phosphoproteomics of cAMP signaling of Bordetella adenylate cyclase toxin in mouse dendritic cells
Schematic depiction of CyaA-induced signaling that would lead to induction of IL-10 production, inhibition of protein translation and deregulation of actin cytoskeleton homeostasis. Elevation of intracellular cAMP concentration due to the catalytic action of internalized AC domain of CyaA provokes activation of the protein kinase A, which performs an inhibitory phosphorylation of the SIK family proteins. This would promote nuclear localization of the transcriptional co-activator CRTC3. In parallel, PKA phosphorylates CREB and the phospho-CREB-CRTC3 complex would activate expression of the IL-10 gene. cAMP-dependent phosphorylation of VASP, presumably by PKA, affects actin cytoskeleton homeostasis. CyaA action further yields inhibition of Akt signaling, thus provoking inhibition of mTOR signaling. Pointed arrowheads indicate an activating effect and flat arrowheads indicate an inhibitory effect under normal physiological conditions. The red color of the arrowhead indicates an inhibitory effect, or interference, resulting from cAMP signaling elicited by the CyaA toxin and the green color indicates an enhancing effect of CyaA/cAMP signaling action. For the broader context of these signaling processes the reader is referred to dedicated reviews on immunity to B. pertussis infections and on CyaA toxin action3,97.
