Calcium- and vitamin D-regulated keratinocyte differentiation

The Recruitment of Phosphatidylinositol 3-Kinase to the E-cadherin-Catenin Complex at the Plasma Membrane Is Required for Calcium-induced Phospholipase C-γ1 Activation and Human Keratinocyte Differentiation

“…Taken together with our previous findings (15,16,55), calcium induced E-cadherin-␤-catenin-p120-catenin complex recruits PI3K via ␤-catenin to the plasma membrane and acti-vates the kinase. PLC-␥1 activated by PIP 3 produced by PI3K in the plasma membrane triggers keratinocyte differentiation through increasing intracellular calcium concentration.…”

“…Diacylglycerol remains in the inner layer of the plasma membrane. IP 3 diffuses through the cytosol and binds to the IP 3 receptors in the endoplasmic reticulum and Golgi causing the intracellular calcium rise, which triggers keratinocyte differentiation (15,16,55). In cultured human or mouse keratinocytes activities of PI3K and PLC-␥1 are induced by calcium within minutes and further stimulated up to 1 h before the onset of keratinocyte differentiation.…”

Correlation of Protease-Activated Receptor-1 With Differentiation Markers in Squamous Cell Carcinoma of the Head and Neck and Its Implication in Lymph Node Metastasis

“…Although MAPK activation induced by PKC-␣ is usually involved in cell proliferation, PKC-␣ and phospholipase C can also induce differentiation of keratinocytes, the cells that form SCCHN. Activation of PKC-␣ and phospholipase C induces expression of profilaggrin, loricrin, and involucrin, the basic elements that form the cornified envelope in a normal stratified epithelial layer (37). PKC-␣ has also been found to induce G 1 arrest, removing cells from the cell cycle (38).…”

“…They are crosslinked into the insoluble cornified envelope in the calciumsensitive and membrane-bound forms in both mouse and human keratinocytes (41,42). Keratin-1 and -10 are usually considered as early differentiation markers, whereas involucrin, loricrin, transglutaminase-I, and profilaggrin are late markers of kerantinocyte differentiation (37). Expression of involucrin and other differentiation markers can be induced through the PKC-␣ signal transduction pathway.…”

“…PKC-␣, in turn, induces and/or activates members of the AP-1 transcription factor family directly through activation of the MAPK pathway. The MAPK pathway then regulates the expression of genes encoding the proteins involved in cornified envelope formation such as involucrin, transglutaminase-I, and loricrin (37).…”