Ribosomal protein S6 is hyperactivated and differentially phosphorylated in epidermal lesions of patients with psoriasis and atopic dermatitis

Abstract

Background The ribosomal protein S6 is part of the translation machinery and is activated by phosphorylation via the mammalian target of rapamycin pathway, which is activated in psoriatic skin. Objectives To investigate which S6 sites are phosphorylated in psoriasis and atopic dermatitis (AD), and to study whether S6 phosphorylation is associated with inflammation and/or keratinocyte hyperproliferation. Methods Healthy skin and skin lesions of patients with psoriasis and AD were investigated by immunostaining using antibodies that stain proliferating cells, leucocytes and distinct phosphorylated sites of S6. Results All psoriasis and AD lesions revealed abnormal S6 phosphorylation in the epidermis. The extent of S6 phosphorylation was diverse, generally stronger in psoriasis and correlated, in both diseases, with inflammation. S6 showed differential phosphorylation in distinct epidermal layers, which was most pronounced in hyperproliferative regions. Conclusions Differential S6 phosphorylation may have a role in abnormal keratinocyte proliferation/differentiation. What's already known about this topic? Phosphorylation of ribosomal protein S6 is important for the initiation of translation. S6 becomes phosphorylated via the mammalian target of rapamycin pathway, which is activated in psoriatic skin. What does this study add? In psoriasis and atopic dermatitis, S6 phosphorylation is associated with inflammation and epidermal hyperproliferation. S6 is differentially phosphorylated in distinct layers of the diseased epidermis, which may impact on the proliferation/differentiation of keratinocytes.