c-Src-dependent transcriptional activation of TFII-I.
TFII-I is a multifunctional transcription factor that is also involved in signal transduction. Here we show that TFII-I undergoes a c-Src-dependent tyrosine phosphorylation on tyrosine residues 248 and 611 and translocates to the nucleus in response to growth factor signaling. Tyrosine-phosphorylated nuclear TFII-I activates a stably integrated c-fos reporter gene. Withdrawal of signal leads to diminution of nuclear TFII-I, suggesting that the signal-dependent translocation is reversible. Antibodies against either TFII-I or c-Src abrogate growth factor-stimulated activation of c-fos. Consistent with the notion that tyrosine phosphorylation of TFII-I is required for its transcriptional activity, phosphorylation-deficient mutants of TFII-I fail to activate the c-fos promoter. These data demonstrate that TFII-I, through a Src-dependent mechanism, reversibly translocates from the cytoplasm to the nucleus, leading to the transcriptional activation of growth-regulated genes.
Cheriyath
Venugopalan
V
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Desgranges
Zana Patrick
ZP
Roy
Ananda L
AL
D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D014443:Tyrosine; D005982:Glutathione Transferase; D016392:Proto-Oncogene Proteins pp60(c-src)