Macrophage asialoglycoprotein-binding protein (M-ASGP-BP) is a Gal/GalNAc-specific lectin, which functions as an endocytosis receptor. We found that the expression of M-ASGP-BP mRNA in bone marrow cells was induced during the differentiation into macrophages, To investigate the mechanism by which M-ASGP-BP mRNA expression is induced, we used U937 cells as a model. Treatment of U937 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in M-ASGP-BP mRNA expression within 6 h. This induction was completely inhibited by PKC inhibitors, calphostin C, and staurosporine. Furthermore, MAP kinase inhibitors PD98059, but not SB202190, blocked M-ASGP-BP mRNA expression. These data indicate that M-ASGP-BP mRNA expression occurs through the activation of PKC and the MAPK classical pathway in the course of cell differentiation into macrophages.