EGF induces nuclear translocation of STAT2 without tyrosine phosphorylation in intestinal epithelial cells

Signal transducers and activators of transcription (STATs) are cytoplasmic proteins that bind to activated membrane receptors, undergo ligand-dependen t phosphorylation on tyrosine residues, and translocate to the nucleus, whe re they induce transcription of specific genes in response to a variety of ligands, including cytokines and some growth factors. Using immunocytochemi cal and biochemical techniques, we investigated the localization and respon ses of STAT1 and STAT2 to epidermal growth factor (EGF) stimulation in IEC- 6 intestinal epithelial cells and HeLa cells. These studies provide the fir st description of STAT activation and localization in response to EGF in in testinal epithelial cells and some novel findings regarding the activation and localization of STATs in general. These include the following. First, E GF promoted the tyrosine phosphorylation of STAT1 in IEC-6 cells and caused its translocation to the nucleus. Second, in the absence of EGF stimulatio n both STAT1 and STAT2 were localized to the Golgi apparatus ill IEC-6 cell s. Third, EGF caused the translocation of STAT2 to the nucleus in both IEC- 6 and HeLa cells without inducing the tyrosine phosphorylation of STAT2.