Abstract
G-protein-coupled receptors (GPCRs) and their associated heterotrimeric G protein-signaling cascades regulate epidermal stem cell fate. We have previously demonstrated that G-alpha stimulating (Gs) and inhibitory (Gi) proteins regulate downstream cAMP signaling which controls keratinocyte differentiation and proliferation in vitro and in vivo. In particular, Gs inactivation causes an expansion of the stem cell compartment resulting in basal cell carcinoma formation. On the other hand, decreasing cAMP signaling by Gi activation leads to epidermal hyperplasia and unbalanced keratinocyte proliferation and differentiation.
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