Import(ance) of Growth Factors in(to) the Nucleus

P OLYPEPTIDE growth factors (GFs) 1 play a fundamental role during embryogenesis and regeneration (e.g., wound healing) by stimulating proliferation and differentiation of certain cell populations. Some GFs can be responsible also for malignant transformation and tumor growth (e.g., FGF-4: hst1 oncogene). GF receptors (GFRs) are generally known as plasma membrane proteins which “send” signals to the nucleus principally via the MAPK and the JAK-STAT pathways (Karin and Hunter, 1995). However, in the past few years data were accumulating to suggest that, surprisingly, nuclear targeting and action of GFs and GF receptors could occur as well. This alternative or complementary signaling pathway appears to be involved in the induction of cell proliferation. In addition, nuclear GF–GFR complexes may participate in the activation of cell line–specific genes as well. Since by far the largest body of data has been published in relation to FGF-1 and -2 (aFGF and bFGF), we have focused here on the nuclear role of these GFs.