Does GSK-3 provide a shortcut for PI3K activation of Wnt signalling?

Glycogen synthase kinase-3 (GSK-3) is a well-established downstream component of the phosphatidylinositol 3-kinase (PI3K) signalling pathway but is also a key enzyme in negatively regulating the canonical Wnt/ß-catenin signalling pathway. Several recent studies argue that PKB (protein kinase B)-mediated inhibition of GSK-3 leads to ß-catenin accumulation, but whether cross-talk actually exists between these two pathways is controversial. To elucidate the mechanisms of shared signalling components, further studies taking into account different components of the PI3K signalling pathway and different pools of GSK-3 or ß-catenin are required.

An eosinophil immune response characterizes the inflammatory skin disease observed in Tie-2 transgenic mice.

Although mouse models of inflammatory skin diseases such as psoriasis and atopic dermatitis fail to completely phenocopy disease in humans, they provide invaluable tools to examine the molecular and cellular mechanisms responsible for the epidermal hyperplasia, inflammation, and excess angiogenesis observed in human disease. We have previously characterized a tyrosine kinase with immunoglobin-like and epidermal growth factor-like domain-2 (Tie-2) transgenic mouse model of an inflammatory skin disease exhibiting these features. More specifically, we demonstrated that the inflammatory component consisted of increased infiltration of CD3-positive T lymphocytes and mast cells in the skin. Here, we further characterize the inflammatory component in the blood and skin of Tie-2 transgenic mice at cellular and molecular levels. We observed increased numbers of CD3-positive T lymphocytes in the blood and increased infiltration of eosinophils in the skin. Furthermore, we characterized cytokine protein and gene expression in the blood and skin, respectively, and observed the deregulated expression of cytokines associated with Th1 and eosinophil immune responses. Interestingly, treatment of Tie-2 transgenic mice with anti-CD4 antibody appeared to resolve aspects of inflammation but did not resolve epidermal hyperplasia, suggesting an important role for eosinophils in mediating the inflammatory skin disease observed in Tie-2 transgenic mice.