Adhesion-dependency of serum-induced p42/p44 MAP kinase activation is released by retroviral oncogenes.

G1/S transition of the cell cycle is blocked when cells are cultured without cell adhesion, even if nutrients and serum are present. Shift experiments involving transfer from adhesion to suspension cultures have revealed that cell adhesion in the early half of G1 phase is required for induction of DNA synthesis. We found that activation of p42/p44 mitogen-activated protein (MAP) kinases, one of the earliest responses induced by serum stimulation, was also dependent on cell adhesion in rat F2408 and mouse Swiss3T3 fibroblast cell lines, suggesting that MAP kinase activation is a critical step in adhesion-dependent G1 progression. F2408 cell lines transformed by the v-src, v-K-ras, and v-mos oncogenes showed constitutively high MAP kinase activity, even in the absence of serum and cell adhesion, while both serum stimulation and cell adhesion were necessary to induce intensive activation of MAP kinase in a F2408 cell line transformed by the E6 and E7 genes of human papillomavirus type 16, as well as in untransformed F2408.