Figure 2.

The role of cAMP scaffolds in TGF‐β‐induced epithelial‐to‐mesenchymal transition (EMT) in the lung. cAMP, which localizes in specific subcellular microdomains, modulates the activities of downstream effectors PKA and Epacs. PDEs, central players in spatio‐temporal dynamics, hydrolyse cAMP and prevent it from diffusing to other compartments. Expression of PDE4 and PDE8 mRNA expression is significantly up‐regulated by TGF‐β1. A‐kinase anchoring proteins (AKAPs) are a group of scaffolding proteins with the ability to associate with PKA via a short α‐helical structure. Ezrin is associated with PGE₂‐induced β‐catenin transcription. AKAP9 plays a crucial role in E‐cadherin maintenance. AKAP13, known to act as a guanine nucleotide exchange factor for RhoA, may be able to promote αvβ6 integrin‐mediated TGF‐β activation in response to epithelial injury. As main inducing factors, cigarette smoke and air pollution are able to modulate cAMP scaffolds in the lung structural cells. For further details, see text. β₂‐AR, β₂‐adrenoceptor; EP2, prostanoid EP₂ receptor