Involvement of the MAP kinase ERK2 in MUC1 mucin signaling

MUC1 mucin is a receptor-like glycoprotein expressed abundantly in various cancer cell lines as well as in glandular secretory epithelial cells, inclu ding airway surface epithelial cells. The role of this cell surface mucin i n the airway is not known. In an attempt to understand the signaling mechan ism of MUC1 mucin, we established a stable cell line from COS-7 cells expre ssing a chimeric receptor consisting of the extracellular and transmembrane domains of CD8 and the cytoplasmic (CT) domain of MUC1 mucin (CD8/MUC1 cel ls). We previously observed that treatment of these cells with anti-CD8 ant ibody resulted in tyrosine phosphorylation of the CT domain of the chimera. Here we report that treatment of CD8/MUC1 cells with anti-CD8 resulted in activation of extracellular signal-regulated kinase (ERK) 2 as assessed by immunoblotting, kinase assay, and immunocytochemistry. The activation of ER K2 was completely blocked either by a dominant negative Pas mutant or in th e presence of a mitogen-activated protein kinase kinase (MEK) inhibitor. We conclude that tyrosine phosphorylation of the CT domain of MUC1 mucin lead s to activation of a mitogen-activated protein kinase pathway through the R as-MEK-ERK2 pathway. Combined with the existing data by others, it is sugge sted that one of the roles of MUC1 mucin may be regulation of cell growth a nd differentiation via a common signaling pathway, namely the Grb2-Sos-Ras- MEK-ERK2 pathway.