Differential Raf requirement for activation of mitogen-activated protein kinase by growth factors, phorbol esters, and calcium.

摘要: Although a pathway that requires sequential activation of Ras, Raf, and MAP kinase has been proposed as the major mechanism for stimulation mitogen-activated protein (MAP kinase), alternative pathways also exist. A wide variety extracellular stimuli have shown to activate kinase; however, precise mechanisms by which these mediate signaling events not elucidated. Using Balb/c-derived cell line expressing dominant-negative mutant we determined whether Raf is required growth factors, phorbol esters, calcium. Insulin-like factor I (IGF-I), epidermal (EGF), 12,13-dibutyrate activated Ras in both control cells. However, IGF-I was nearly abolished mutant. Stimulation Ca2+ mobilizer thapsigargin inhibited presence In contrast, EGF remained potent stimulators The can be further distinguished differential requirements C. These results suggest calcium, whereas possibly esters may employ Raf-independent activation.