THE ACTIVATION AND COMPOSITION OF FIRE (AN FGF-INDUCIBLE RESPONSE ELEMENT) DIFFER IN A CELL TYPE-SPECIFIC AND GROWTH-FACTOR-SPECIFIC MANNER

The expression of the heparan sulfate proteoglycan, syndecan-1, is ind uced both in keratinocytes and in fibroblasts during development and t issue regeneration. Here we report that in keratinocytes the syndecan- 1 gene was stimulated by EGF but not by FGF-2, In fibroblasts it was s timulated by FGF-2 but not by EGF, Likewise, the recently discovered F GF-inducible response element (FiRE) on the gene of syndecan-1 was sti mulated by FGF-2 in fibroblasts and by EGF in keratinocytes, but not v ice vel sn. The FIRE has two binding sites for an activator protein-1 (AP-1), one for an FGF-inducible nuclear factor (FIN-1) and one for an upstream stimulatory factor-1 (USF-1), The growth factor-stimulated b inding of these transcription factors, as well as their requirement fo r FiRE activation, varied between the two cell types. First, although AP-ls were required for activation of FIRE in both cell types, the bin ding of AP-1 to FiRE was increased by growth factor-stimulation only i n fibroblasts and not in keratinocytes, Secondly, FiRE did not bind FI N-1 nor needed the FIN-1 binding site for EGF-stimulated activation in keratinocytes, in contrast to the FGF-stimulated activation of FiRE i n fibroblasts, Thirdly, EGF, which did not activate FIRE in fibroblast s, failed to activate FIN-1 in these cells. Finally, an USF-1 binding site that was necessary for activation of FIRE in keratinocytes was no t needed in fibroblasts, These data suggest mechanisms by which member s of the EGF- and FGF-families can differentially stimulate transcript ion through AP-1 regulated elements in a cell type-specific manner.