Differential Activation of Mitogen-activated Protein Kinase and S6 Kinase Signaling Pathways by 12-O-Tetradecanoylphorbol-13-acetate (TPA) and Insulin EVIDENCE FOR INVOLVEMENT OF A TPA-STIMULATED PROTEIN-TYROSINE KINASE

摘要: Abstract AG-18, an inhibitor of protein-tyrosine kinases, was employed to study the role tyrosine-phosphorylated proteins in insulin- and phorbol ester-induced signaling cascades. When incubated with Chinese hamster ovary cells overexpressing insulin receptor, AG-18 reversibly inhibited insulin-induced tyrosine phosphorylation receptor substrate-1, minimal effects either on autophosphorylation or Shc64. Under these conditions, insulin-stimulated ribosomal protein S6, while no inhibition activation mitogen-activated kinase (MAPK) MAPK detected. In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced S6 were by AG-18. This correlated TPA-stimulated several proteins, most prominent ones being pp114 pp120. We conclude that Tyr-phosphorylated substrate-1 is main upstream regulator p70, whereas seems be activated primarily through adaptor molecule Shc. TPA-induced mediated MAPK/p90 cascade. A key element this pathway AG-18-sensitive kinase.