Activation of an enhancer on the syndecan-1 gene is restricted to fibroblast growth factor family members in mesenchymal cells.
Fibroblast growth factors (FGFs) induce a variety of biological effects on different cell types. They activate a number of genes, including immediate-early genes, such as the transcription factors Fos and Jun, which are also common targets for other tyrosine kinase receptor-activating growth factors. Here we describe a secondary far-upstream enhancer on the syndecan-1 gene that is activated only by members of the FGF family in NIH 3T3 cells, not by other receptor tyrosine kinase-activating growth factors (e.g., epidermal growth factor, platelet-derived growth factor, insulin-like growth factor, or serum). This FGF-inducible response element (FiRE) consists of a 170-bp array of five DNA motifs which bind two FGF-inducible Fos-Jun heterodimers, one inducible AP-2-related protein, a constitutively expressed upstream stimulatory factor, and one constitutive 46-kDa transcription factor. Mutational analysis showed that both AP-1 binding motifs are required, but not sufficient, for FiRE activation. Moreover, agents such as 12-O-tetradecanoylphorbol-13-acetate, okadaic acid, or forskolin, which are known to activate AP-1 complexes and AP-1-driven promoters, fail to activate FiRE. However, FiRE can be activated by the tyrosine kinase phosphatase inhibitor orthovanadate. Taken together, this data implies a differential activation of growth factor-initiated signaling on AP-1-driven regulatory elements.
Jaakkola
P
P
Turku Centre for Biotechnology, BioCity, Finland.
Vihinen
T
T
Määttä
A
A
Jalkanen
M
M
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D004742:Enhancer Elements, Genetic / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D013002:Somatomedins / Q000494:pharmacology; D053668:Syndecan-1; D053667:Syndecans; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor; D011509:Proteoglycans; C508242:Sdc1 protein, mouse; D013002:Somatomedins; D053668:Syndecan-1; D053667:Syndecans; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor