Fibroblast growth factors 1 and 2 differently activate MAP kinase in Xenopus oocytes expressing fibroblast growth factor receptors 1 and 4

The mitogen-activated protein kinase (MAP kinase) signalling cascade activa ted by fibroblast growth factors (FGF1 and FCF2) was analysed in a model sy stem, Xenopus oocytes, expressing fibroblast growth factor receptors (FGFR1 and FGFR4). Stimulation of FGFP1 by FGF1 or FGF2 and FGFR4 by FGF1 induced a sustained phosphorylation of extracellular signal-regulated protein kina se 2 (ERK2) and meiosis reinitiation. In contrast FGFR4 stimulation by FGF2 induced an early transient activation of ERK2 and no meiosis reinitiation. FGFR4 transduction cascades were differently activated by FGF1 and FGF2. E arly phosphorylation of ERK2 was blocked by the dominant negative from of g rowth factor-bound protein 2 (Grb2) and Ras, for FGF1-FGFR4 and FGF2-FGFR4. The phosphatidylinositol 3-kinase (PI3 kinase) inhibitors wortmannin and L Y294002 only prevented the early ERK2 phosphorylation triggered by FGF2-FGF R4 but not by FGF1-FGFR4. ERK2 phosphorylation triggered by FGFF4 depended on the Grb2/Ras pathway and also involved PI3 kinase in a time-dependent ma nner. (C) 2001 Elsevier Science B.V. All rights reserved.