Expression, localization, and activity of glycogen synthase kinase 3β during mouse skin tumorigenesis

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Abstract
Glycogen synthase kinase 3 (GSK‐3) is a protein kinase that plays essential roles in the control of several developmental, metabolic, and apoptotic processes. Owing to its negative actions on several oncogenic insults, it has been considered a putative functional tumor suppressor. We studied the expression, activity, and localization of GSK‐3β during the process of chemically induced two‐stage mouse skin carcinogenesis and also in the tumors generated upon subcutaneous injection of Akt‐transformed keratinocytes. We found that GSK‐3 activity was downregulated at the later stages of promotion by tyrosine 216 dephosphorylation and serine 9 phosphorylation. The data obtained with Akt‐transformed keratinocytes clearly suggested the involvement of Akt in serine 9 phosphorylation of GSK‐3β. Finally, besides functional inactivation, significant basal activity of GSK‐3β was detected in all cases, indicating that this enzyme provides essential functions to malignant keratinocytes.