title: Fibroblast growth factor receptor-induced phosphorylation of STAT1 at the Golgi apparatus without translocation to the nucleus.
abstract: STAT transcription factors signal from the plasma membrane to the nucleus in response to growth factors and cytokines, but little is known about activation of STAT1 from intracellular sites. Here we show that transient transfection of COS cells with fibroblast growth factor receptors (FGFRs) led to ligand-independent phosphorylation of the receptors, including intracellular immature forms. FGF-independent activation of STAT1 was demonstrated at the Golgi apparatus where it was colocalized with FGFRs. Both FGFR1 and FGFR2 induced strong phosphorylation of STAT1 causing redistribution of the Golgi apparatus, while FGFR3 and FGFR4 induced less phosphorylation of STAT1 and little or no redistribution of the Golgi apparatus. Upon expression of a cytosolic mutant of FGFR4 lacking the transmembrane as well as the extracellular region (CytR4), STAT1 was phosphorylated and transferred to the nucleus. The results indicate that immature forms of FGFRs form incomplete signaling complexes on Golgi membranes trapping phospho-STAT1 on this organelle.
authors.affiliation: Facultad de Ciencias, Departamento de Bioquímica y Biología Molecular, Universidad de Valladolid, Valladolid, Spain. luciac@bio.uva.es
authors.forename: Lucía
authors.initials: L
authors.lastname: Citores
authors.forename: Ling
authors.initials: L
authors.lastname: Bai
authors.forename: Vigdis
authors.initials: V
authors.lastname: Sørensen
authors.forename: Sjur
authors.initials: S
authors.lastname: Olsnes
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D019556:COS Cells; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D050794:STAT1 Transcription Factor