Journal
FEBS LETTERS
Volume 536, Issue 1-3, Pages 30-34Publisher
WILEY
DOI: 10.1016/S0014-5793(03)00005-X
Keywords
smad; bone morphogenetic protein-2; fibrobast growth factor; fibrobast growth factor receptor type-1; PC12 cells
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We previously reported that bone morphogenetic protein (BMP)-2 augments fibroblast growth factor (FGF)-induced neuronal differentiation of PC12 cells by selectively upregulating FGF receptor (FGFR)-1 expression. Here we describe the underlying mechanism. BMP-2 activated Smad proteins in PC12 cells. Overexpression of Smad7 or Smad1, inhibitory and receptor-regulated isoforms, respectively, suppressed or enhanced BMP-2-induced upregulation of FGFR-I expression. Smad 7 also inhibited the FGF-induced PC12 differentiation. Our findings indicate that activation of a Smad signaling pathway is required for upregulation of FGFR-1 expression by BMP-2 and for the synergistic induction of PC12 differentiation by BMP-2 and FGF. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
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