Molecular signaling in the regulation of mucins.

Mucins are large, highly glycosylated proteins involved in the protection of epithelia. The 20 different mucins show a diverse and highly regulated distribution among different epithelia. Most of the studies on mucin regulation done to date have been on the membrane mucins MUC1 and MUC4 and the gel-forming mucins. Multiple mechanisms have been implicated in that regulation, including examples at the transcriptional, transcript stabilization and post-translational levels. Several signaling pathways have been demonstrated to be involved, most frequently the canonical Erk MAP kinase pathway, but also the cytokine-JAK-STAT pathway and TGFbeta-SMAD pathways. Diversity in Erk signaling is achieved through multiple activation mechanisms and multiple downstream transcriptional factors that are affected. Given the still limited amount of information available on regulation of most of the mucins, other mechanisms and pathways are likely to be uncovered in the future.