Role of ERK/MAP kinase in mitogenic interaction between ACTH and FGF2 in mouse Y1 adrenocortical tumor cells

In G(0)/G(1) cell cycle-arrested Y1 adrenocortical cells FGF2 is a strong m itogen, whereas ACTH(39) can be a weak mitogen or a strong anti-mitogenic a gent. Phosphorylated ERK1/2-MAP kinases are undetectable by Western and imm unocitochemistry assay in G(0)/G(1)-arrested Y1 adrenal cells. Cell entry i nto S phase linearly correlates with migration of phosphorylated ERK to nuc leus. FGF2 rapid and strongly triggers transient phosphorylation of ERK1/2, whereas ACTH(39) is a poor ERK1/2 activator. But, the MEK1 inhibitor, PD98 059 (50 muM), inhibits cFos and cyclin D1 induction and DNA synthesis stimu lation by both ACTH(39) and FGF2, suggesting that ERK1/2 activation mediate s the strong and the weak mitogenic effect of, respectively, FGF2 and ACTH( 39). In addition, ACTH(39) antagonizes the FGF2 mitogenic effect keeping un touched ERK1/2 activation, c-Fos and cyclin D1 induction.