Keratins, the intermediate filament proteins of epithelial cells, connect to desmosomes, the cell-cell adhesion structures at the surface membrane. Among the various intermediate filament (IF) proteins, cytokeratin 8 (CK8) is especially remarkable as it is produced early in embryogenesis, is the only type-II CK occurring in many simple epithelial cells, and can also be synthesized in certain non-epithelial cells (1). Keratin 8 and 18 (CK8/18) are the major keratin pair in simple-type epithelia, as found in the liver, pancreas, and intestine (2). While K8/K18 are essential for maintaining structural integrity, there is accumulating evidence indicating that they also exert non-mechanical functions. It has been reported that K8/K18-free hepatocytes from K8-null mice are more sensitive to Fas-mediated apoptosis, in line with an increased Fas density at the cell surface and an altered c-Flip regulation of the anti-apoptotic ERK1/2 signaling pathway (3).
EGFR1 Signaling Pathway
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